Addiction Biology

Cover image for Vol. 21 Issue 1

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Rainer Spanagel, Editor for North America: Markus Heilig

Impact Factor: 5.359

ISI Journal Citation Reports © Ranking: 2014: 1/18 (Substance Abuse); 43/290 (Biochemistry & Molecular Biology)

Online ISSN: 1369-1600

Associated Title(s): Addiction


  1. 1 - 100
  2. 101 - 155
  1. Original Articles

    1. You have full text access to this OnlineOpen article
      Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature

      Luisa Lo Iacono, Alessandro Valzania, Federica Visco-Comandini, Eleonora Aricò, Maria Teresa Viscomi, Luciano Castiello, Diego Oddi, Francesca R. D'Amato, Elisa Bisicchia, Olga Ermakova, Stefano Puglisi-Allegra and Valeria Carola

      Article first published online: 12 FEB 2016 | DOI: 10.1111/adb.12373

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      This study provides novel insights into the mechanism by which childhood maltreatment heightens risk for relapse in cocaine-dependent individuals. We modeled childhood maltreatment by exposing juvenile mice to a threatening social experience. This influenced the propensity to reinstate cocaine seeking after periods of withdrawal in adulthood. We found that this phenotype was associated with greater blood coagulation and impairments in brain microvasculature. Notably, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine seeking in these mice.

    2. Perseveration of craving: effects of stimuli conditioned to drugs of abuse versus conventional reinforcers differing in demand

      Rémi Martin-Fardon and Friedbert Weiss

      Article first published online: 10 FEB 2016 | DOI: 10.1111/adb.12374

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      Here we showed that behavior guided by associations between environmental stimuli and drugs of abuse are characterized by perseverating, apparently highly extinction-resistant reward seeking, whereas behavior controlled by stimuli associated with conventional reward extinguishes rapidly in the absence of primary reinforcement. Reward seeking elicited by stimuli associated with natural reward can, however, become perseverative during physiological deprivation states. Possibly, perseverating drug seeking engages mechanisms overlapping with those that have evolved to promote alleviation of physiological deprivation to secure survival.

    3. White matter alterations in cocaine users are negatively related to the number of additionally (ab)used substances

      Anne Marije Kaag, Guido A. van Wingen, Matthan W. A. Caan, Judith R. Homberg, Wim van den Brink and Liesbeth Reneman

      Article first published online: 10 FEB 2016 | DOI: 10.1111/adb.12375

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      Polysubstance use is a widespread phenomenon among cocaine users. In the current diffusion tensor imaging study, we demonstrated that the degree of white matter alterations is related to the number of different types of substances used (cocaine, alcohol and marijuana). These alterations are suggested to explain why treatment outcome is poorer among polysubstance users compared with single-substance users.

    4. Cannabis use and symptoms of anxiety in adolescence and the moderating effect of the serotonin transporter gene

      Roy Otten, Anja C. Huizink, Karin Monshouwer, Hanneke E. Creemers and Simone Onrust

      Article first published online: 10 FEB 2016 | DOI: 10.1111/adb.12372

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      This study examined the relationship between cannabis use and symptoms of anxiety by taking a developmental molecular-genetic perspective with a focus on a polymorphism involved in the regulation of serotonin. Results showed that cannabis use is associated with an increase in symptoms of anxiety, but only in carriers of the short allele of the 5-HTTLPR genotype, thereby suggesting that the link between cannabis use and anxiety is conditional on an individuals' genetic makeup.

    5. Alcohol withdrawal induces long-lasting spatial working memory impairments: relationship with changes in corticosterone response in the prefrontal cortex

      Gaelle Dominguez, Catherine Belzung, Christophe Pierard, Vincent David, Nadia Henkous, Laurence Decorte, Nicole Mons and Daniel Beracochea

      Article first published online: 10 FEB 2016 | DOI: 10.1111/adb.12371

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      We showed here (1) that long-lasting glucocorticoids dysregulation in the prefrontal cortex (PFC) is responsible for the maintenance of working memory (WM) deficits and phosphorylated CREB alterations in alcohol-withdrawn (1 and 6 weeks) mice previously submitted to a 6-months alcohol consumption (12% v/v); (2) that a systemic injection of metyrapone (which inhibits corticosterone synthesis) before testing restored both WM and PFC-phosphorylated CREB activity in withdrawn mice; and (3) that the intra-PFC blockade of mineralocorticoid receptors by spironolactone reverses the withdrawal-associated WM deficits.

    6. Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration

      María Antón, Francisco Alén, Raquel Gómez de Heras, Antonia Serrano, Francisco Javier Pavón, Juan Carlos Leza, Borja García-Bueno, Fernando Rodríguez de Fonseca and Laura Orio

      Article first published online: 9 FEB 2016 | DOI: 10.1111/adb.12365

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      In this study, we reported a beneficial role for the lipid oleoylethanolamide (OEA) to treat alcohol binge drinking because of its antiinflammatory, antioxidant, neuroprotective and antidepressant-like effects. Pre#x2010;treatment with OEA during binging episodes blocked the expression of HMGB1/TLR4 cell danger signaling and inhibited the nuclear factor-kappa B-related cascade of proinflammatory mediators, affording protection against ethanol-induced lipid peroxidation and apoptosis in frontal cortex. Additionally, OEA blocked the rise in blood corticosterone induced by alcohol binge and had antidepressant-like actions during early withdrawal.

    7. Cannabidiol disrupts the reconsolidation of contextual drug-associated memories in Wistar rats

      Cristiane Ribeiro de Carvalho and Reinaldo Naoto Takahashi

      Article first published online: 1 FEB 2016 | DOI: 10.1111/adb.12366

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      This study examines the effects of an acute injection of cannabidiol (CBD) post-reactivation on reconsolidation of drug associated memories in rats. CBD persistently disrupts the reconsolidation of morphine-CPP and suppresses subsequent morphine-CPA to the same context (see figure). Our findings suggest CBD may be a potentially pharmacologic adjunct to cue exposure cognitive behavior therapy used for developing novel treatments for weakening memories induced by drugs of abuse and subsequently reducing the risk of withdrawal and relapse.

    8. Medications development for the treatment of alcohol use disorder: insights into the predictive value of animal and human laboratory models

      Megan M. Yardley and Lara A. Ray

      Article first published online: 1 FEB 2016 | DOI: 10.1111/adb.12349

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      The primary goal of this paper was to provide a perspective on medications development for alcohol use disorder along with an illustrative review of the literature encompassing preclinical, human laboratory, and clinical trials. This review highlights the marked need for standardization of testing procedures at each level of medications development, including standard protocols for experimental paradigms, population characteristics (in both animal and human studies), and analyses of predefined primary and secondary outcomes. Such standardization would allow us to more effectively integrate results from various studies using both critical reviews of the literature as well as quantitative studies and advance treatment development in this area.

    9. You have full text access to this OnlineOpen article
      Adult rat cortical thickness changes across age and following adolescent intermittent ethanol treatment

      Ryan P. Vetreno, Richard Yaxley, Beatriz Paniagua, G. Allan Johnson and Fulton T. Crews

      Article first published online: 1 FEB 2016 | DOI: 10.1111/adb.12364

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      Magnetic resonance imaging and histology was used to determine the effect of ageing and adolescent binge ethanol exposure on cortical thickness in adult rats. We discovered that the cerebral cortex continues to undergo age-associated cortical thinning and expansion into adulthood, which was altered by prior adolescent binge ethanol exposure. These data reveal that the cerebral cortex continues to undergo refinement into adulthood and that adolescent binge ethanol treatment alters adult cortical thickness that might contribute to behavioural dysfunction.

    10. Characterization of white matter integrity deficits in cocaine-dependent individuals with substance-induced psychosis compared with non-psychotic cocaine users

      Taylor S. Willi, Alasdair M. Barr, Kristina Gicas, Donna J. Lang, Fidel Vila-Rodriguez, Wayne Su, Allen E. Thornton, Olga Leonova, Chantelle J. Giesbrecht, Ric M. Procyshyn, Alexander Rauscher, William G. MacEwan, William G. Honer and William J. Panenka

      Article first published online: 1 FEB 2016 | DOI: 10.1111/adb.12363

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      Similarity in psychotic presentation between substance-induced psychosis and schizophrenia spectrum disorders suggests that similar neural deficits contribute to the expression of psychosis across these disorders. Diffusion tensor imaging was employed to investigate white matter abnormalities in a cocaine-associated psychosis group (n = 24) compared with a cocaine-dependent non-psychotic group (n = 43). Voxels within white matter tracts of fronto-temporal, fronto-thalamic and interhemispheric pathways had significantly lower fractional anisotropy values in the psychosis group, similar to pathways altered in schizophrenia spectrum disorders.

    11. Expression of functional cannabinoid CB2 receptor in VTA dopamine neurons in rats

      Hai-Ying Zhang, Ming Gao, Hui Shen, Guo-Hua Bi, Hong-Ju Yang, Qing-Rong Liu, Jie Wu, Eliot L. Gardner, Antonello Bonci and Zheng-Xiong Xi

      Article first published online: 1 FEB 2016 | DOI: 10.1111/adb.12367

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      The presence of neuronal CB2 receptor in the brain has been controversial. The present study provides convincing evidence demonstrating that CB2 gene (mRNA) and receptors are not only expressed in midbrain dopamine neurons, but also functionally modulate dopamine neuronal excitability, striatal dopamine release and intravenous cocaine self-administration. In addition, cocaine self-administration up-regulates CB2 gene expression in dopamine neurons, suggesting that brain CB2 receptor may constitute a new target in medication development for treatment of addiction or other dopamine-related central nervous system disorders.

    12. Oxytocin inhibits ethanol consumption and ethanol-induced dopamine release in the nucleus accumbens

      Sebastian T. Peters, Michael T. Bowen, Kathrin Bohrer, Iain S. McGregor and Inga D. Neumann

      Article first published online: 25 JAN 2016 | DOI: 10.1111/adb.12362

      Here, we describe the possible mechanisms underlying the inhibitory effect of oxytocin on voluntary ethanol self-administration. Central infusion of oxytocin prevented the ethanol-induced activation of the mesolimbic dopamine system, specifically the rise in dopamine release within the nucleus accumbens both after acute and chronic ethanol administration in rats. Although these, together with our recent findings, suggest that OXT may interfere with ethanol consumption and ethanol-induced dopamine release in the nucleus accumbens via interaction with δ subunit-containing GABAA receptors, further molecular mechanisms of the action of oxytocin need to be revealed before an oxytocin-related treatment option for alcoholism can be considered.

    13. Intra-cerebral and intra-nasal melanocortin-4 receptor antagonist blocks withdrawal hyperalgesia in alcohol-dependent rats

      Emily A. Roltsch Hellard, Renata A. Impastato and Nicholas W. Gilpin

      Article first published online: 24 JAN 2016 | DOI: 10.1111/adb.12360

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      Alcohol-dependent rats exhibit thermal hyperalgesia, which is abolished by alcohol drinking, bolus alcohol, and intra-ventricular and intra-nasal melanocortin 4 receptor (MC4R) antagonists. These manipulations did not affect thermal nociception in non-dependent drinkers and alcohol-naïve controls, suggesting that alcohol dependence produces neuroadaptations in brain MC4R systems. These results suggest that brain MC4R systems may be an effective therapeutic target for reducing nociception in alcohol-dependent organism.

    14. Loss of δ-GABAA receptor-mediated tonic currents in the adult prelimbic cortex following adolescent alcohol exposure

      Samuel W. Centanni, Elizabeth J. Burnett, Heather Trantham-Davidson and L. Judson Chandler

      Article first published online: 24 JAN 2016 | DOI: 10.1111/adb.12353

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      The adolescent prefrontal cortex (PFC) is particularly vulnerable to developmental insults from alcohol abuse. Using a rat model of adolescent alcohol exposure, the present study examined the effect of adolescent alcohol exposure on GABAergic neurotransmission in the adult PFC. We show that adult rats exposed to alcohol during adolescence exhibit prolonged deficits in tonic GABAergic currents. These observations may contribute to deficits in decision-making and behavioral control in adulthood.

    15. Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala

      Florence P. Varodayan, Michal Bajo, Neeraj Soni, George Luu, Samuel G. Madamba, Paul Schweitzer and Marisa Roberto

      Article first published online: 20 JAN 2016 | DOI: 10.1111/adb.12369

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      Endogenous cannabinoid/type 1 cannabinoid receptor (eCB/CB1) signaling modulates basolateral nucleus of the amygdala (BLA) GABA release, a mechanism critical for anxiety-driven alcohol drinking and relapse. Our electrophysiological results show that BLA GABA release was increased by CB1 activation and decreased by CB1 blockade; chronic ethanol exposure blunted these effects, suggesting a functional impairment of eCB/CB1 signaling. Also, CB1 blockade and acute ethanol increased GABA release in an additive manner, suggesting that they have different presynaptic sites of action.

    16. Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit

      Lucía Vaquero, Estela Cámara, Frederic Sampedro, José Pérez de los Cobos, Francesca Batlle, Josep Maria Fabregas, Joan Artur Sales, Mercè Cervantes, Xavier Ferrer, Gerardo Lazcano, Antoni Rodríguez-Fornells and Jordi Riba

      Article first published online: 19 JAN 2016 | DOI: 10.1111/adb.12356

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      Using a lottery task and magnetic resonance imaging, we demonstrate that cocaine-dependent patients show functional and structural brain abnormalities. While patients show hypersensitivity to incentives in subcortical regions, they fail to engage the prefrontal cortex following adverse behavioral outcomes. Structurally, they show increased gray and white matter in reward-processing areas but decreased white matter integrity in antero-posterior association bundles. These findings suggest that abnormal fronto-subcortical function, hypertrophy and hyper-connectivity within the reward circuit, and decreased connectivity outside this network, characterize cocaine addiction.

    17. Frontal cortex gray matter volume alterations in pathological gambling occur independently from substance use disorder

      Evangelos Zois, Falk Kiefer, Tagrid Lemenager, Sabine Vollstädt-Klein, Karl Mann and Mira Fauth-Bühler

      Article first published online: 15 JAN 2016 | DOI: 10.1111/adb.12368

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      The first morphometric investigation to examine gray matter volume alterations in pathological gamblers controlling for the impact of substance use disorder by comparing non-comorbid gamblers and two comorbid groups – alcohol and polysubstance. One hundred and seven patients were included in the analysis and 98 healthy controls. We demonstrated specific frontal-cortex gray-matter deficits in gamblers with and without substance use disorder comorbidity. Those frontal alterations are associated with addicted gambling behavior independent of toxic substance effects.

    18. Brain reactivity to alcohol and cannabis marketing during sobriety and intoxication

      Elizabeth B. de Sousa Fernandes Perna, Eef L. Theunissen, Kim P. C. Kuypers, Elisabeth A. Evers, Peter Stiers, Stefan W. Toennes, Jurriaan Witteman, Wim van Dalen and Johannes G. Ramaekers

      Article first published online: 14 JAN 2016 | DOI: 10.1111/adb.12351

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      We examined brain reactivity to alcohol and cannabis marketing during sobriety as well as intoxication and compared brain network activation and implicit cognition during both states. Our findings suggest that alcohol and drug marketing can trigger similar brain responses to those that occur during drug use and drug craving, but the reinforcing strength of drug marketing cues appear to be reduced following alcohol and cannabis intoxication.

    19. Cocaine craving during protracted withdrawal requires PKCε priming within vmPFC

      Bailey W. Miller, Melissa G. Wroten, Arianne D. Sacramento, Hannah E. Silva, Christina B. Shin, Philip A. Vieira, Osnat Ben-Shahar, Tod E. Kippin and Karen K. Szumlinski

      Article first published online: 14 JAN 2016 | DOI: 10.1111/adb.12354

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      Incubated cocaine-craving during protracted withdrawal in rats was associated with time-dependent changes in protein kinase C (PKC) epsilon priming within the ventromedial aspect of the prefrontal cortex (vmPFC). The local infusion of an inhibitor of PKC epsilon translocation blocked cue-elicited drug-seeking during later, but not earlier, withdrawal. These data argue an important role for PKC epsilon-dependent signaling within vmPFC for heightened craving during protracted cocaine withdrawal.

    20. You have full text access to this OnlineOpen article
      Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol-induced reward in rodents

      Daniel Vallöf, Lisa Ulenius, Emil Egecioglu, Jörgen A. Engel and Elisabet Jerlhag

      Article first published online: 14 JAN 2016 | DOI: 10.1111/adb.12355

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      In contrast to the common view of the function of gut–brain peptides, such as neuromedin U (NMU), to regulate food intake, a novel role in reinforcement mediation has been implied. We found that central administration of NMU attenuated alcohol-induced locomotor stimulation, accumbal dopamine release and conditioned place preference as well as decreased alcohol intake in rodents. Our data suggest that NMU analogues deserve to be evaluated as novel treatment of alcohol use disorder, a major health-care challenge, in humans.

    21. Frontostriatal circuits, resting state functional connectivity and cognitive control in internet gaming disorder

      Kai Yuan, Dahua Yu, Chenxi Cai, Dan Feng, Yangding Li, Yanzhi Bi, Jixin Liu, Yi Zhang, Chenwang Jin, Linling Li, Wei Qin and Jie Tian

      Article first published online: 14 JAN 2016 | DOI: 10.1111/adb.12348

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      Reduced resting-state functional connectivity between the right caudate and the right dorsolateral prefrontal cortex was negatively correlated with more errors during incongruent condition in Stroop task in IGD subjects.

    22. Posterior hippocampal regional cerebral blood flow predicts abstinence: a replication study

      Bryon Adinoff, Thomas S. Harris, Hong Gu and Elliot A. Stein

      Article first published online: 11 JAN 2016 | DOI: 10.1111/adb.12361

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      The posterior hippocampus (pHp) is linked to striatal-limbic circuits involved with craving. We recently reported increased pHp ASL-assessed basal regional cerebral blood flow (rCBF) predicted days to cocaine relapse following residential treatment. In this secondary analysis, increased pHp rCBF (by single photon emission computerized tomography) successfully predicted 30-day point prevalence substance use 60 days following residential treatment in an independent group of cocaine-dependent participants. This replicative finding that suggests heightened pHp activation predicts future substance use, possibly reflecting a neural susceptibility to drug cues.

    23. Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area

      John W. Dutton III, Hu Chen, Chang You, Mark S. Brodie and Amy W. Lasek

      Article first published online: 11 JAN 2016 | DOI: 10.1111/adb.12358

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      We tested anaplastic lymphoma kinase (ALK) inhibitors in a mouse model of binge drinking and found that ALK inhibition reduced binge-like alcohol consumption. ALK appears to act in the ventral tegmental area to regulate binge-like drinking and may affect ethanol consumption through modulation of dopamine D2 receptor activity. Our results indicate that treatment with small molecule inhibitors of ALK might be a viable therapeutic strategy to reduce binge drinking in individuals with alcohol use disorders.

    24. Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence

      Alena Becker, Martina Kirsch, Martin Fungisai Gerchen, Falk Kiefer and Peter Kirsch

      Article first published online: 11 JAN 2016 | DOI: 10.1111/adb.12352

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      Neurobiological theories of addiction highlight the role of the prefrontal cortex not only through its engagement in executive functions but also through monitoring the mesolimbic reward system. We investigated the neural activation and connectivity underlying non-drug reward anticipation in alcohol dependence. Alcohol-dependent patients showed increased activation of the ventral striatum, along with decreased frontostriatal connectivity, during the anticipation of monetary reward. This diminished frontostriatal connectivity was associated with increased craving, as measured by the Obsessive Compulsive Drinking Scale.

    25. The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

      Omkar L. Patkar, Arnauld Belmer, Joan Y. Holgate, Josephine R. Tarren, Masroor R. Shariff, Michael Morgan, Matthew J. Fogarty, Mark C. Bellingham, Selena E. Bartlett and Paul M. Klenowski

      Article first published online: 11 JAN 2016 | DOI: 10.1111/adb.12359

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      In this study, we show that the antihypertensive drug pindolol reduces ethanol consumption in mice following long-term binge-like intake. Pindolol did not have non-specific effects on locomotor activity, ethanol sensitivity or consumption of the natural reward sucrose. We also show that pindolol reduces excitatory post-synaptic current frequency in naïve mice but increases excitatory post-synaptic current frequency in long-term ethanol consuming mice. Combined, these results demonstrate that pindolol represents a novel treatment option of the management of alcohol use disorders. Figure 1 highlights the key finding of the study.

    26. Topiramate and motivational enhancement therapy for cannabis use among youth: a randomized placebo-controlled pilot study

      Robert Miranda Jr., Hayley Treloar, Alexander Blanchard, Alicia Justus, Peter M. Monti, Thomas Chun, Robert Swift, Jennifer W. Tidey and Chad J. Gwaltney

      Article first published online: 11 JAN 2016 | DOI: 10.1111/adb.12350

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      Results of this double-blind, placebo-controlled pilot study showed that topiramate, combined with motivational enhancement therapy, reduced how much cannabis adolescents smoked when they used but it did not affect abstinence rates. Significant increases in abstinence rates were observed in both medication conditions. Topiramate was poorly tolerated by many youths, however, and the magnitude of its effect on cannabis use was modest, which calls to question the clinical importance of these findings.

    27. Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner

      Reginald Cannady, Kristen R. Fisher, Caitlin Graham, Jesse Crayle, Joyce Besheer and Clyde W. Hodge

      Article first published online: 6 JAN 2016 | DOI: 10.1111/adb.12357

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      Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Here, we show that low-dose alcohol self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 in rat central amygdala and that CaMKII-dependent activation of AMPA receptors in the amygdala increases the positive reinforcing effects of alcohol. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction.

    28. Striatal dopaminergic reward response relates to age of first drunkenness and feedback response in at-risk youth

      Barbara J. Weiland, Robert A. Zucker, Jon-Kar Zubieta and Mary M. Heitzeg

      Article first published online: 5 JAN 2016 | DOI: 10.1111/adb.12341

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      The mesolimbic dopamine system is hypothesized to play a role in vulnerability to substance use disorders. Using multi-modal methods (functional magnetic resonance imaging and positron emission tomography), we tested whether young adult male subjects at high risk for substance use disorders based on family history and early drunkenness had differences in response to monetary rewards compared with controls. We found heightened striatal dopamine response in high-risk male subjects during positron emission tomography. This was further associated with age of first drunkenness, suggesting it may represent a neurobiological risk phenotype.

    29. Disruption of hippocampal synaptic transmission and long-term potentiation by psychoactive synthetic cannabinoid ‘Spice’ compounds: comparison with Δ9-tetrahydrocannabinol

      Alexander F. Hoffman, Matthew D. Lycas, Jakub R. Kaczmarzyk, Charles E. Spivak, Michael H. Baumann and Carl R. Lupica

      Article first published online: 5 JAN 2016 | DOI: 10.1111/adb.12334

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      Three synthetic cannabinoids commonly found in illicit ‘Spice’ compounds were evaluated for their acute effects on hippocampal synaptic transmission and compared with THC. Although the compounds varied in their potency, both THC and the synthetic cannabinoids strongly suppressed glutamate release and disrupted hippocampal long-term potentiation. These actions will likely contribute to adverse consequences of synthetic cannabinoids on cognitive and behavioral function and highlight the need to further understand the neurobiological effects of these rapidly emerging new psychoactive substances.

    30. Activation of the ventral and dorsal striatum during cue reactivity in Internet gaming disorder

      Lu Liu, Sarah W. Yip, Jin-Tao Zhang, Ling-Jiao Wang, Zi-Jiao Shen, Ben Liu, Shan-Shan Ma, Yuan-Wei Yao and Xiao-Yi Fang

      Article first published online: 5 JAN 2016 | DOI: 10.1111/adb.12338

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      For the individuals with Internet gaming disorder (IGD), cue-induced activity within the left ventral striatum was correlated negatively with cue-induced craving, whereas positive associations were found between activations within the dorsal striatum (right putamen, pallidum, and left caudate) and duration of IGD.

    31. Cocaine self-administration induces changes in synaptic transmission and plasticity in ventral hippocampus

      Madhusudhanan M. Keralapurath, Sherri B. Briggs and John J. Wagner

      Article first published online: 22 DEC 2015 | DOI: 10.1111/adb.12345

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      Changes in synaptic transmission and long-term potentiation (LTP) occur in the CA1 region of the ventral hippocampus following extended access to cocaine self-administration in rats. Increased AMPA/NMDA ratio, increased basal-evoked excitatory transmission, and a decreased capacity to express LTP were observed following 3–5 weeks of withdrawal following a cocaine short access/long access experience. These results indicate that withdrawal following extended access to cocaine self-administration can result in a chronically potentiated state in the CA1 region of the ventral hippocampus.

    32. Loss of brain graph network efficiency in alcohol dependence

      Zsuzsika Sjoerds, Steven M. Stufflebeam, Dick J. Veltman, Wim Van den Brink, Brenda W. J. H. Penninx and Linda Douw

      Article first published online: 22 DEC 2015 | DOI: 10.1111/adb.12346

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      In this study, we applied graph theory on resting state functional magnetic resonance imaging to investigate the complex brain network in alcohol dependent patients. Patients with alcohol dependence showed lower global brain network efficiency and strength with longer alcohol dependence duration, and with more severe alcohol use. Alcohol use severity was not associated with brain network efficiency in healthy controls. Longer alcohol-dependence duration was additionally associated with reduced clustering coefficient and weighted degree in ventromedial and anterior striatum.

    33. Re-exposure to morphine-associated context facilitated long-term potentiation in the vSUB-NAc glutamatergic pathway via GluN2B-containing receptor activation

      Yi-Jing Li, Xing-Jie Ping, Chong Qi, Fang Shen, Lin-Lin Sun, Xiao-Wei Sun, Fei-Fei Ge, Guo-Gang Xing and Cai-Lian Cui

      Article first published online: 22 DEC 2015 | DOI: 10.1111/adb.12343

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      Re-exposure to the morphine-associated context facilitated the long-term potentiation induction in the vSUB-nucleus accumbens (NAc) pathway. Intra-NAc shell injection of GluN2B–N-methyl-d-aspartate receptor antagonist RO25-6981 prevented the long-term potentiation facilitation. The inhibition of the GluN2B–N-methyl-d-aspartate receptors in the vSUB-NAc pathway prevented morphine conditioned place preference expression.

    34. Brain connectivity and psychiatric comorbidity in adolescents with Internet gaming disorder

      Doug Hyun Han, Sun Mi Kim, Sujin Bae, Perry F. Renshaw and Jeffrey S. Anderson

      Article first published online: 22 DEC 2015 | DOI: 10.1111/adb.12347

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      This study measured brain functional connectivity in 151 adolescents with and without compulsive video game playing. Subjects with Internet gaming disorder showed higher connectivity between sensory cortex, salience network, and dorsal attention network, possibly adaptive training effects of gaming, but also increased connectivity between default mode and executive networks, which may relate to psychiatric comorbidity. The findings were not explained by depression or ADHD in the study population.

    35. Genetic and pharmacological manipulation of glyoxalase 1 regulates voluntary ethanol consumption in mice

      Katherine M. J. McMurray, Preetpal S. Sidhu, James M. Cook, Leggy A. Arnold and Abraham A. Palmer

      Article first published online: 22 DEC 2015 | DOI: 10.1111/adb.12333

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      We have discovered that gene glyoxalase 1 (Glo1) is a novel regulator of ethanol consumption. Mice overexpressing Glo1 voluntarily consumed more ethanol. Furthermore, Glo1 knockdown mice and mice treated with a pharmacological inhibitor of GLO1 consumed less ethanol. None of our manipulations of GLO1 altered water, sucrose or saccharin consumption nor did they alter the duration of loss of righting reflex or footslips on a balance beam. Therefore, pharmacological inhibition of GLO1 may constitute a novel target for treatment of alcohol use disorders.

    36. Chronic EtOH effects on putative measures of compulsive behavior in mice

      Anna K. Radke, Nicholas J. Jury, Adrina Kocharian, Catherine A. Marcinkiewcz, Emily G. Lowery-Gionta, Kristen E. Pleil, Zoe A. McElligott, Jessica M. McKlveen, Thomas L. Kash and Andrew Holmes

      Article first published online: 21 DEC 2015 | DOI: 10.1111/adb.12342

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      Footshock punishment suppressed operant responding for ethanol (EtOH). Punished-suppression was absent in mice with a history of chronic exposure to EtOH vapors. Loss of sensitivity to punishment following chronic EtOH exposure was associated with increased NMDA receptor (GluN1, GluN2A subunits) expression and NMDA receptor synaptic currents in the medial orbitofrontal cortex. These findings demonstrate a link between cortical glutamate signaling and increased compulsive-like EtOH-seeking.

    37. Prefrontal functional connectivity measured with near-infrared spectroscopy during smoking cue exposure

      Agnes M. Kroczek, Florian B. Haeussinger, Andreas J. Fallgatter, Anil Batra and Ann-Christine Ehlis

      Article first published online: 21 DEC 2015 | DOI: 10.1111/adb.12344

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      We investigated cue reactivity in smokers during smoking cue exposure by means of changes in the prefrontal cortex (assessed by functional near-infrared spectroscopy) and subjective craving ratings. During the time course of the cue exposure, smokers showed increased craving ratings. Changes in craving (range) correlated with hemodynamics in the orbitofrontal cortex (OFC), while the reported minimum craving for each subject correlated with hemodynamics in the dorsolateral prefrontal cortex (dlPFC). Connectivity between OFC and dlPFC was increased in smokers compared with controls.

  2. Invited Reviews

    1. Recent developments in the behavioural and pharmacological enhancement of extinction of drug seeking

      Rose Chesworth and Laura H. Corbit

      Article first published online: 21 DEC 2015 | DOI: 10.1111/adb.12337

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      This review summarizes and evaluates recent developments in the behavioural and pharmacological facilitation of extinction of drug seeking, in both preclinical models and clinical trials. We highlight areas where promising preclinical models have not yet been integrated into current clinical practice but, if applied, could improve upon existing behavioural and pharmacological methods. The clinical translation of preclinical behavioural and pharmacological findings has had limited success, and suggestions for methodological improvements are made based on a theoretical understanding of extinction learning.

  3. Original Articles

    1. Altered white matter integrity in whole brain and segments of corpus callosum, in young social drinkers with binge drinking pattern

      Kathleen W. Smith, Fabien Gierski, Judith Andre, Nicholas G. Dowell, Mara Cercignani, Mickaël Naassila and Theodora Duka

      Article first published online: 21 DEC 2015 | DOI: 10.1111/adb.12332

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      Mean fractional anisotropy (FA), measured at two time points 8–12 months apart, shows reduced efficiency of white matter connectivity in the body of corpus callosum, in male, but not female, binge drinkers compared with non-binge drinkers. Lower FA in the prefrontal segment of corpus callosum was associated with higher binge score in men and worse spatial working memory both in men and in women.

    2. Excessive alcohol consumption increases mortality in later life: a genetic analysis of the health in men cohort study

      Osvaldo P. Almeida, Kieran McCaul, Graeme J. Hankey, Bu B. Yeap, Jonathan Golledge and Leon Flicker

      Article first published online: 8 DEC 2015 | DOI: 10.1111/adb.12340

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      We found a triangular association between ADH1B rs1229984 G>A polymorphism, regular alcohol intake and mortality. The findings indicate that excessive alcohol use is a direct cause of death in later life and that there is no obvious survival advantage associated with mild to moderate drinking. Health messages regarding the safe use of alcohol may benefit from taking notice of these results.

    3. Rev-erbα modulates the hypothalamic orexinergic system to influence pleasurable feeding behaviour in mice

      Céline A. Feillet, Claire Bainier, Maria Mateo, Aurea Blancas-Velázquez, Nora L. Salaberry, Jürgen A. Ripperger, Urs Albrecht and Jorge Mendoza

      Article first published online: 2 DEC 2015 | DOI: 10.1111/adb.12339

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      •Orexin (ORX) neurons regulate metabolic and hedonic feeding

      •The clock gene Rev-Erb-alpha has an important role in the regulation of ORX signalling

      •Rev-Erb-alpha mutations lead to an increase in hypothalamic ORXergic activity and in food-reward behaviour in mice

    4. Voluntary ethanol consumption reduces GABAergic neuroactive steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) in the amygdala of the cynomolgus monkey

      Matthew C. Beattie, Antoniette M. Maldonado-Devincci, Patrizia Porcu, Todd K. O'Buckley, James B. Daunais, Kathleen A. Grant and A. Leslie Morrow

      Article first published online: 2 DEC 2015 | DOI: 10.1111/adb.12326

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      Neuroactive steroids such as [3α, 5α]3-hydroxy-pregnan-20-one (3α,5α-THP) enhance the GABAergic effects of ethanol, and chronic ethanol consumption reduces plasma and brain 3α,5α-THP levels. We explored the relationship between 3α,5α-THP levels in amygdala sub-regions and voluntary ethanol consumption in the cynomolgus monkey following 12 months of daily self-administration. Prolonged ethanol consumption reduced cellular 3α,5α-THP immunoreactivity in the lateral amygdala and the basolateral amygdala that was inversely correlated with average daily ethanol intake. Amygdala 3α,5α-THP appears to regulate ethanol consumption in nonhuman primates.

    5. Extended nicotine self-administration increases sensitivity to nicotine, motivation to seek nicotine and the reinforcing properties of nicotine-paired cues.

      Kelly J. Clemens, Belinda P. P. Lay and Nathan M. Holmes

      Article first published online: 2 DEC 2015 | DOI: 10.1111/adb.12336

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      An array of pharmacological and environmental factors influences the development and maintenance of tobacco addiction. The present study demonstrated that with extended training, rats become more sensitive to changing doses of nicotine, more motivated to work for nicotine and increasingly controlled by nicotine-associated cues and that the partial nicotine receptor agonist varenicline has dissociable effects on responding for nicotine versus a nicotine-paired cue. Together, these results show that nicotine seeking is controlled by multiple sources and, therefore, highly resistant to change.

    6. Ethanol affects limbic and striatal presynaptic glutamatergic and DNA methylation gene expression in outbred rats exposed to early-life stress

      Maria Vrettou, Linnea Granholm, Aniruddha Todkar, Kent W. Nilsson, Åsa Wallén-Mackenzie, Ingrid Nylander and Erika Comasco

      Article first published online: 27 NOV 2015 | DOI: 10.1111/adb.12331

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      Using a rodent maternal separation (MS) model, the study assessed the effect of early life stress (ELS) and adult voluntary ethanol drinking on expression of Vesicular Glutamate Transporter (Vglut) and DNA methylation-related genes in the mesocorticolimbic circuit and dorsal striatum. The results indicated interaction effects between ELS and ethanol consumption in a gene-dependent and region-dependent manner, mirrored by changes in the epigenetic machinery.

    7. Reduced activity in functional networks during reward processing is modulated by abstinence in cocaine addicts

      Víctor Costumero, Juan Carlos Bustamante, Patricia Rosell-Negre, Paola Fuentes, Juan José Llopis, César Ávila and Alfonso Barrós-Loscertales

      Article first published online: 27 NOV 2015 | DOI: 10.1111/adb.12329

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      Independent component analysis was performed in functional magnetic resonance imaging data to investigate differences between cocaine addicts and healthy controls in the response to erotic images.

      Cocaine addicts displayed diminished modulation of the left frontoparietal network in response to erotic pictures. The modulation of the left frontoparietal network by unpredicted erotic images in cocaine addicts correlated with length of abstinence.

      These results suggest that cocaine addiction contributes to reduce sensitivity to rewarding stimuli and that abstinence may mitigate this effect.

    8. Individual differences in orexin-I receptor modulation of motivation for the opioid remifentanil

      Kirsten A. Porter-Stransky, Brandon S. Bentzley and Gary Aston-Jones

      Article first published online: 24 NOV 2015 | DOI: 10.1111/adb.12323

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      Using a within-session behavioral economic procedure, we observed in rats robust individual differences in motivation for the short-acting opioid remifentanil. High takers exhibited greater drug consumption at low cost, continued to work for drug despite increases in price (low demand elasticity), and withstood greater electrical shock to continue self-administering remifentanil. Antagonism of orexin 1 receptors reduced free consumption, demand elasticity, and cue-induced reinstatement of drug seeking in low takers but not in high takers, which exhibit an addition-like phenotype.

    9. Glucocorticoid receptor but not mineralocorticoid receptor mediates the activation of ERK pathway and CREB during morphine withdrawal

      Javier Navarro-Zaragoza, M. Luisa Laorden and M. Victoria Milanés

      Article first published online: 24 NOV 2015 | DOI: 10.1111/adb.12328

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      Glucocorticoid receptor (GR) blockade attenuated ERK and CREB phosphorylation and the tyrosine hydroxylase (TH) expression induced by morphine withdrawal. In contrast, no changes were seen after MR blockade. Finally, GR and MR blockades did not alter the morphine withdrawal induced increase seen both in DA turnover and DA metabolite production, in the NAcc. These results show that not only ERK and CREB phosphorylation but also TH expression in the NTS are modulated by GR signalling.

    10. Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long-term cocaine self-administration

      Ping Gao, Jules H. W. Limpens, Sabine Spijker, Louk J. M. J. Vanderschuren and Pieter Voorn

      Article first published online: 24 NOV 2015 | DOI: 10.1111/adb.12330

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      After 10 and 60 days self-administration of cocaine, increased expression was found for six immediate early genes (IEGs) in dorsal (DS) and ventral striatum (VS) and 10 IEGs in medial prefrontal cortex (mPFC). No major differences were found between IEG expression patterns after 10 or 60 days. These steady changes appeared associated with stable self-administration rather than the total amount of cocaine consumed. Thus, sustained impulses to IEG regulation during prolonged cocaine self-administration may evoke neuroplastic changes underlying compulsive drug use.

    11. You have full text access to this OnlineOpen article
      Differential gene expression patterns between smokers and non-smokers: cause or consequence?

      Jacqueline M. Vink, Rick Jansen, Andy Brooks, Gonneke Willemsen, Gerard van Grootheest, Eco de Geus, Jan H. Smit, Brenda W. Penninx and Dorret I. Boomsma

      Article first published online: 22 NOV 2015 | DOI: 10.1111/adb.12322

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      A genome-wide gene expression study for smoking was conducted. To explore the causes or consequences of smoking behavior, data of 743 smokers, 1686 never-smokers and 890 ex-smokers were used, as well as a sample of monozygotic twins discordant for smoking. Gene expression patterns of smokers significantly differed from non-smokers. Differences were mainly direct consequences of smoking, and largely reversible after smoking cessation. In addition, some DNA variants were identified that may influence smoking behavior via the mediating gene expression.

    12. Autophosphorylation of alpha isoform of calcium/calmodulin-dependent kinase II regulates alcohol addiction-related behaviors

      Zofia Mijakowska, Kacper Łukasiewicz, Magda Ziółkowska, Michał Lipiński, Anna Trąbczyńska, Żaneta Matuszek, Szymon Łęski and Kasia Radwanska

      Article first published online: 16 NOV 2015 | DOI: 10.1111/adb.12327

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      The development of addiction is associated with a dysregulation of glutamatergic transmission in the brain reward circuit. α isoform of calcium/calmodulin-dependent kinase II (αCaMKII) is one of the key proteins that regulate glutamatergic synapses. Using α CaMKII autophosphorylation-deficient mutant mice, we show that αCaMKII autophosphorylation is involved in development of alcohol addiction-related behaviors including an increased motivation for alcohol, persistent alcohol seeking during withdrawal, and alcohol consumption on relapse.

    13. Chronic intermittent alcohol disrupts the GluN2B-associated proteome and specifically regulates group I mGlu receptor-dependent long-term depression

      Tiffany A. Wills, Anthony J. Baucum II, Katherine M. Holleran, Yaoyi Chen, Johanna G. Pasek, Eric Delpire, David L. Tabb, Roger J. Colbran and Danny G. Winder

      Article first published online: 8 NOV 2015 | DOI: 10.1111/adb.12319

    14. Noradrenergic inputs from locus coeruleus to posterior ventral tegmental area are essential to support ethanol reinforcement

      Gajanan P. Shelkar, Santosh Kumar, Praful S. Singru, Nishikant K. Subhedar and Dadasaheb M. Kokare

      Article first published online: 8 NOV 2015 | DOI: 10.1111/adb.12321

      The addictive behavior of the rat to self-administer ethanol in the posterior-ventral tegmental area was significantly promoted by noradrenergic agents. While silencing of the noradrenergic neurons of the locus coeruleus suppressed the craving for ethanol, the addiction was fully reinstated by noradrenergic agents. We provide behavioral as well as neuroanatomical evidences demonstrating that two-way communication between locus coeruleus and ventral tegmental area is essential for ethanol reinforcement and addiction.

    15. α2A-Adrenergic receptor polymorphisms and mRNA expression levels are associated with delay discounting in cocaine users

      Michael M. Havranek, Lea M. Hulka, Eve Tasiudi, Christoph Eisenegger, Matthias Vonmoos, Katrin H. Preller, Rainald Mössner, Markus R. Baumgartner, Erich Seifritz, Edna Grünblatt and Boris B. Quednow

      Article first published online: 8 NOV 2015 | DOI: 10.1111/adb.12324

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      Investigating the interplay between cocaine use and point mutations in the α2A-adrenergic receptor (ADRA2A) gene on delay discounting (DD), we found significant interactions for three linked ADRA2A single nucleotide polymorphisms (rs1800544, rs521674, and rs602618) revealing significantly steeper DD in cocaine users (n = 129) but not in stimulant-naïve controls (n = 94) carrying the rare alleles, respectively (genotype effect in cocaine users: **p < 0.01). Positive scores indicate low reward impulsivity, whereas negative scores reflect elevated reward impulsivity (z-transformed means [+/–SEM] corrected for age and verbal IQ).

    16. Peripheral and prefrontal stress system markers and risk of relapse in alcoholism

      Sara K. Blaine, Dongju Seo and Rajita Sinha

      Article first published online: 5 NOV 2015 | DOI: 10.1111/adb.12320

      Forty alcohol-dependent patients underwent a laboratory experiment with exposure to neutral, alcohol, and stress cues and a separate fMRI scan with similar cue exposure. The neutral-relaxed state cortisol to ACTH ratio (cort:ACTH) was significantly associated with ventromedial prefrontal cortex (VmPFC) hyperreactivity to neutral-relaxing cues, and VmPFC hypoactivation in response to alcohol and stress cues. The odds of relapse were more strongly predicted by the dysfunctional VmPFC response to cues than the cort:ACTH ratio in a joint model of relapse risk.

    17. Pulling habits out of rats: adenosine 2A receptor antagonism in dorsomedial striatum rescues meth-amphetamine-induced deficits in goal-directed action

      Teri M. Furlong, Alva S. A. Supit, Laura H. Corbit, Simon Killcross and Bernard W. Balleine

      Article first published online: 30 OCT 2015 | DOI: 10.1111/adb.12316

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      We investigated the influence of a methamphetamine (METH)-paired context on decision-making in rats. Goal-directed action was sensitive to outcome devaluation in a saline-paired context but not in a METH-paired context, even when negative feedback was provided. Reduced c-Fos immunoreactivity was seen in dorsomedial striatum in the METH context. Intrastriatal infusion of an adenosine receptor antagonist restored sensitivity to negative feedback in the METH context. These results suggest that drug exposure alters decision-making by downregulation of the circuitry mediating goal-directed action.

    18. You have full text access to this OnlineOpen article
      The monoamine stabilizer (−)-OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats

      Kristin Feltmann, Ida Fredriksson, Malin Wirf, Björn Schilström and Pia Steensland

      Article first published online: 14 OCT 2015 | DOI: 10.1111/adb.12304

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      We have previously established that the monoamine stabilizer OSU6162 attenuates alcohol-mediated behaviors in long-term drinking rats and that it has potential as a medication for alcohol use disorder (AUD). The present study indicates that OSU6162 counteracts dopamine deficits in the nucleus accumbens in long-term drinking rats and that OSU6162 is not rewarding on its own. Together with the compound's beneficial side-effect profile, the present study merits evaluation of OSU6162's clinical efficacy to attenuate alcohol use in AUD patients.

    19. Genome-wide association study of body mass index in subjects with alcohol dependence

      Renato Polimanti, Huiping Zhang, Andrew H. Smith, Hongyu Zhao, Lindsay A. Farrer, Henry R. Kranzler and Joel Gelernter

      Article first published online: 12 OCT 2015 | DOI: 10.1111/adb.12317

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      To investigate alterations in the regulation of body mass that occur in the context of alcohol dependence (AD), we performed a genome-wide association study (GWAS) of body mass index (BMI) in 5546 subjects with AD. Three of the GWS loci identified (rs200889048, rs12490016 and rs1630623) were not previously reported by GWAS of BMI in the general population, and two of them raise interesting hypotheses: rs12490016, a regulatory variant located within LINC00880, and rs1630623, a regulatory variant related to ALDH1A1.

    20. Brain substrates of social decision-making in dual diagnosis: cocaine dependence and personality disorders

      Antonio Verdejo-Garcia, Juan Verdejo-Román, Natalia Albein-Urios, José M. Martínez-González and Carles Soriano-Mas

      Article first published online: 6 OCT 2015 | DOI: 10.1111/adb.12318

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      Patients with cocaine dependence and personality disorders performing a social economic decision-making task display reduced activation of the insula and the anterior cingulate cortex regions, which typically held the emotional aspects of social offers, and greater activation of frontal and temporal regions, which is negatively associated with emotion recognition skills.

    21. Trait and state binge eating predispose towards cocaine craving

      Royi Barnea, Liza Bekker, Noa Zifman, Asaf Marco, Gal Yadid and Aron Weller

      Article first published online: 30 SEP 2015 | DOI: 10.1111/adb.12315

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      We found that the degree of binge eating like-behavior and the state and trait combination predicted the pattern of craving for self-administered cocaine after it ceased to be available. Lower levels of dopamine D2 receptors in the prefrontal cortex were correlated with increased drug craving. Our findings show that restricted access to an attractive diet is a risk factor, particularly in trait binge eaters, because they persistently failed to cease seeking cocaine.

    22. Family history of alcoholism is related to increased D2/D3 receptor binding potential: a marker of resilience or risk?

      Anika A. H. Alvanzo, Gary S. Wand, Hiroto Kuwabara, Dean F. Wong, Xiaoqiang Xu and Mary E. McCaul

      Article first published online: 29 SEP 2015 | DOI: 10.1111/adb.12300

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      This study examined differences in striatal dopamine between young adult social drinkers with positive (FHP) and negative (FHN) family history of alcohol use disorder using positron emission tomography imaging. Baseline [11C]raclopride binding potential (BPND) was generally higher in FHP compared with FHN subjects. Although there were no differences in amphetamine-induced change in binding potential (ΔBPND), the expected positive relationship between ΔBPND and positive subjective drug effects was disrupted in FHP subjects who also reported more pronounced negative subjective drug effects.

    23. Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption

      Mariangela Pucci, Maria Vittoria Micioni Di Bonaventura, Maria Elena Giusepponi, Adele Romano, Monica Filaferro, Mauro Maccarrone, Roberto Ciccocioppo, Carlo Cifani and Claudio D'Addario

      Article first published online: 21 SEP 2015 | DOI: 10.1111/adb.12303

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      Binge eating is triggered by a unique interaction between dieting and stress. We observed that rats subjected to cycles of food restriction and then exposed to frustration stress showed binge eating. We provide data on target gene expression regulation (CRF and N/OFQ system genes) via epigenetic mechanisms, suggesting differential roles in selected brain regions. In the VTA, CRF system gene upregulation in response to stress might lead to the increase of high palatable food consumption through modulation of reward mechanisms.

    24. Environmental enrichment facilitates cocaine-cue extinction, deters reacquisition of cocaine self-administration and alters AMPAR GluA1 expression and phosphorylation

      Jamie M. Gauthier, Amy Lin, Bríd Á. Nic Dhonnchadha, Roger D. Spealman, Heng-Ye Man and Kathleen M. Kantak

      Article first published online: 18 SEP 2015 | DOI: 10.1111/adb.12313

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      Brief 4-h periods of environmental enrichment (EE) scheduled both 24 h before and immediately after weekly cocaine-cue extinction training significantly facilitated the rate of extinction learning and deterred reacquisition of cocaine self-administration. EE alone or extinction alone was ineffective, as was EE scheduled at individual time points. The combination of EE with extinction training altered pSer845GluA1 expression in both the ventromedial prefrontal cortex and the basolateral amygdala. Thus, EE might be a useful adjunct to extinction therapy by enabling neuroplasticity that deters relapse to cocaine self-administration.

    25. Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood–brain barrier

      Marta Rodríguez-Arias, Sandra Montagud-Romero, Ana Rubio-Araiz, María A. Aguilar, Elena Martín-García, Roberto Cabrera, Rafael Maldonado, Francesca Porcu, María Isabel Colado and José Miñarro

      Article first published online: 16 SEP 2015 | DOI: 10.1111/adb.12301

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      The current study shows for the first time that mice exposed to RSD undergo significant changes in BBB structure. RSD during adolescence induces a marked reduction in expression of the tight junction protein claudin-5 and an increase in basal laminin degradation (reflected by a decrease in laminin and collagen-IV expression) in the NAc in adulthood. Concomitantly, there is an increase in IgG extravasation, indicating that social defeat increases BBB permeability, probably through alterations in structural proteins.

    26. Rats quit nicotine for a sweet reward following an extensive history of nicotine use

      Carmen Huynh, Justine Fam, Serge H. Ahmed and Kelly J. Clemens

      Article first published online: 16 SEP 2015 | DOI: 10.1111/adb.12306

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      Drug use may be exacerbated in environments that lack access to alternative, rewarding outcomes. Here, we examine whether rats will continue to self-administer nicotine when allowed the option to ingest a sweet solution reward. Using a discrete-trial, forced-choice procedure, rats demonstrate a clear preference for saccharin over nicotine at all times, despite variations in reward concentration, or after an extensive nicotine history. This finding is consistent with past studies examining choice over a variety of potent drugs of abuse.

    27. Involvement of lateral septum in alcohol's dopamine-elevating effect in the rat

      Susanne Jonsson, Julia Morud, Rosita Stomberg, Mia Ericson and Bo Söderpalm

      Article first published online: 14 SEP 2015 | DOI: 10.1111/adb.12297

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      The common effect of drugs of abuse to increase extracellular dopamine (DA) levels in the mesolimbic DA system has been linked to positive and reinforcing experiences of drug consumption and is presumably of importance for continued use, dependence and addiction. Using in vivo microdialysis, it was demonstrated that blocking the generation of action potentials in lateral septum, using tetrodotoxin, prevented a DA increase in nucleus accumbens after accumbal ethanol perfusion. These results provide evidence implicating the lateral septum in the reinforcing effects of ethanol.

    28. Reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing

      Ann-Kathrin Stock, Moritz Mückschel and Christian Beste

      Article first published online: 11 SEP 2015 | DOI: 10.1111/adb.12296

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      We investigated whether an acute strong alcohol intoxication alters how proprioceptive information is processed during response selection. Using a Simon task with crossed hand position versus parallel hand position, we found an alcohol-induced reversal of effects. Specific changes in the neurophysiological data suggest that processes related to the preparation and execution of the motor response underlie these modulations. In short, proprioceptive information does not seem to be properly integrated in response selection processes during acute alcohol intoxication as found in binge drinking.

    29. Methadone enhances human influenza A virus replication

      Yun-Hsiang Chen, Kuang-Lun Wu, Ming-Ta Tsai, Wei-Hsien Chien, Mao-Liang Chen and Yun Wang

      Article first published online: 8 SEP 2015 | DOI: 10.1111/adb.12305

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      Growing evidence has indicated that opioids enhance replication of human immunodeficiency virus and hepatitis C virus in cells. However, it is unknown whether opioids can enhance replication of human influenza A virus (H1N1). Here, methadone, but not morphine or buprenorphine, was shown to enhance H1N1 replication in human lung epithelial cells. In addition, treatment with methadone significantly increased H1N1 replication in mouse lungs. Our data suggest that methadone might increase influenza A virus infection in people receiving methadone treatment.

    30. Rat-strain dependent changes of dendritic and spine morphology in the hippocampus after cocaine self-administration

      Abraham Selvas, Santiago M. Coria, Asta Kastanauskaite, Isabel Fernaud-Espinosa, Javier DeFelipe, Emilio Ambrosio and Miguel Miguéns

      Article first published online: 2 SEP 2015 | DOI: 10.1111/adb.12294

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      We studied cocaine effects on CA1 dendrites and dendritic spines in Lewis vs. Fischer 344 rats. Lewis had underlying significantly larger dendritic diameters but lower spine density than Fischer 344 rats. After cocaine self-administration, proximal dendritic size, spine density and the percentage of larger spines were increased in Lewis rats. By contrast, Fischer 344 rats showed decreased spine head volumes. Our findings suggest that genetic differences could play a key role in cocaine-induced structural plasticity in CA1 pyramidal neurons.

    31. You have full text access to this OnlineOpen article
      The glucagon-like peptide 1 receptor agonist liraglutide attenuates the reinforcing properties of alcohol in rodents

      Daniel Vallöf, Paola Maccioni, Giancarlo Colombo, Minja Mandrapa, Julia Winsa Jörnulf, Emil Egecioglu, Jörgen A. Engel and Elisabet Jerlhag

      Article first published online: 25 AUG 2015 | DOI: 10.1111/adb.12295

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      Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, is an incretin peptide and is therefore approved for treatment of diabetes type II. The present experiments show that liraglutide suppressed alcohol-induced reward in mice, reduced alcohol intake and prevented relapse drinking in outbreed rats as well as decreased operant self-administration of alcohol in selectively bred Sardinian alcohol-preferring rats. Collectively, these data suggest that GLP-1 receptor agonists could be tested for treatment of alcohol dependence in humans.

    32. The new stimulant designer compound pentedrone exhibits rewarding properties and affects dopaminergic activity

      Ji-Young Hwang, Jun-Sub Kim, Ji-Hwan Oh, Sa-Ik Hong, Shi-Xun Ma, Yang-Hee Jung, Yong-Hyun Ko, Seok-Yong Lee, Hyoung-Chun Kim and Choon-Gon Jang

      Article first published online: 19 AUG 2015 | DOI: 10.1111/adb.12299

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      Cathinone derivatives are new recreational drugs known to produce psychostimulant effects. Here, we investigated the effects of pentedrone, a type of cathinone derivative, on the dopaminergic system. We also evaluated the addictive potential of pentedrone using conditioned place preference and self-administration. We found that pentedrone affects dopaminergic activity in PC-12 cells and shows addictive property in mice and rats. Collectively, these data suggest that the addictive properties of pentedrone may be due to its effects on the dopaminergic system.

    33. Ethanol drives aversive conditioning through dopamine 1 receptor and glutamate receptor-mediated activation of lateral habenula neurons

      Wanhong Zuo, Rao Fu, Frederic Woodward Hopf, Guiqin Xie, Kresimir Krnjević, Jing Li and Jiang-Hong Ye

      Article first published online: 18 AUG 2015 | DOI: 10.1111/adb.12298

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      Very low concentration (1.4 mM) of ethanol strongly enhances spike firing in lateral habenula (LHb) in vitro, by an action mediated in part by glutamate receptors, dopamine D1 receptors and cAMP signaling. By contrast, much higher concentrations of ethanol activate ventral tegmental dopamine neurons. Manipulation of LHb activity in vivo altered conditioned place aversion and preference induced respectively by ethanol at 0.25 g and 2 g/kg (i.p.). Thus, ethanol activation of LHb neurons may contribute to its aversive properties.

  4. Special Issues

    1. Transient CNS responses to repeated binge ethanol treatment

      Natalie M. Zahr, Torsten Rohlfing, Dirk Mayer, Richard Luong, Edith V. Sullivan and Adolf Pfefferbaum

      Article first published online: 18 AUG 2015 | DOI: 10.1111/adb.12290

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  5. Original Articles

    1. Functional significance of subjective response to alcohol across levels of alcohol exposure

      Spencer Bujarski, Kent E. Hutchison, Nicole Prause and Lara A. Ray

      Article first published online: 10 AUG 2015 | DOI: 10.1111/adb.12293

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      Neurobiological theories have characterized addiction as pathological motivation, dissociated from hedonic reward. This study tested this claim in humans by examining the relationship between subjective responses and craving during an i.v. alcohol challenge in light-to-moderate drinkers, heavy drinkers or alcohol dependents. Consistent with the prediction of diminished positive reinforcement in dependence, this study showed that stimulation/hedonic reward from alcohol did not predict craving in alcohol dependents, whereas stimulation was dose-dependently associated with and predicted craving among non-dependent heavy drinkers.

    2. Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST

      Kristen E. Pleil, Christa M. Helms, Jon R. Sobus, James B. Daunais, Kathleen A. Grant and Thomas L. Kash

      Article first published online: 29 JUL 2015 | DOI: 10.1111/adb.12289

    3. Effects of repeated yohimbine administration on reinstatement of palatable food seeking: involvement of dopamine D1-like receptors and food-associated cues

      Kevin T. Ball, Leah Miller, Christopher Sullivan, Ashleigh Wells, Olivia Best, Brittany Cavanaugh, Taylor Copus, Nathan Corrigan, Shaina Hawkins, Krista Kobbe, Ashley Schoener, Johnathan Steiger and Lauren Vieweg

      Article first published online: 29 JUL 2015 | DOI: 10.1111/adb.12287

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      No systematic studies on the effects of chronic stress on relapse to food or drug seeking have been conducted. We report that reinstatement of palatable food seeking by the pharmacological stressor yohimbine and pellet priming were both potentiated in rats with a history of chronic yohimbine exposure relative to non-chronically stressed rats. Moreover, a dopamine D1-like receptor antagonist combined with repeated yohimbine injections attenuated this effect. Thus, chronic stress may increase vulnerability to relapse via a D1-like receptor-mediated mechanism.

    4. Substance P in the anterior thalamic paraventricular nucleus: promotion of ethanol drinking in response to orexin from the hypothalamus

      Jessica R. Barson, Kinning Poon, Hui Tin Ho, Mohammad I. Alam, Lilia Sanzalone and Sarah F. Leibowitz

      Article first published online: 29 JUL 2015 | DOI: 10.1111/adb.12288

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      Intermittent-access 20% ethanol drinking may involve neuropeptide communication between the hypothalamus and the anterior paraventricular thalamus (aPVT). Ethanol drinking is hypothesized to be promoted by orexin/hypocretin (OX) from the hypothalamus acting at the orexin 2 receptor (OX2R) on substance P (SP)-containing neurons in the aPVT. Ethanol drinking has also been shown to increase levels of OX, which would further excite this aPVT pathway. In contrast, SP in the posterior paraventricular thalamus (pPVT) promotes sucrose intake.

    5. KAT2B polymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex

      Eric O. Johnson, Dana B. Hancock, Joshua L. Levy, Nathan C. Gaddis, Grier P. Page, Cristie Glasheen, Nancy L. Saccone, Laura J. Bierut and Alex H. Kral

      Article first published online: 23 JUL 2015 | DOI: 10.1111/adb.12286

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      Intronic single nucleotide polymorphism (rs9829896) in the K(lysine) acetyltransferase 2B (KAT2B) gene was significantly associated with drug abuse in African Americans (AAs) (P = 4.63 × 10−8) and independently replicated in AAs (P = 0.0019): meta-analysis P = 3.93 × 10−10. Using dorsolateral prefrontal cortex data from the BrainCloud cohort, rs9829896-C was associated with reduced KAT2B expression in AAs (n = 113, P = 0.050). KAT2B encodes a transcriptional regulator in the cyclic adenosine monophosphate and dopamine signaling pathways. Rs9829896-C was associated with expression of genes in these pathways: reduced CREBBP (P = 0.011) and increased OPRM1 expression (P = 0.016) in AAs.

    6. Adolescent-onset of cocaine use is associated with heightened stress-induced reinstatement of cocaine seeking

      Wai Chong Wong and Michela Marinelli

      Article first published online: 23 JUL 2015 | DOI: 10.1111/adb.12284

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      Adolescent onset of cocaine use has long-term consequences into adulthood, despite a prolonged drug-free period. Thus, adult rats that self-administered cocaine as adolescents show greater reinstatement of cocaine-seeking behavior, compared with adult rats that self-administered cocaine as adults. Reinstatement of cocaine-seeking behavior was induced by stress, and these findings were consistent for a variety of stressors and experimental conditions.

    7. Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

      Sinead E. Shortall, Clare H. Spicer, Francis J. P. Ebling, A. Richard Green, Kevin C. F. Fone and Madeleine V. King

      Article first published online: 16 JUL 2015 | DOI: 10.1111/adb.12283

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      Mephedrone users often employ repeated administration due to its short duration of action. This study investigated the role of dopamine and 5-HT in mephedrone-induced hyperactivity and hypothermia following repeated administration. Mephedrone increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity and hypothermia were attenuated by 5-HT depletion, and by 5-HT1B or 5-HT1A receptor antagonism, respectively. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake plays a pivotal role in mephedrone-induced hyperactivity and hypothermia.

    8. Disrupted white matter structural connectivity in heroin abusers

      Yan Sun, Gui-Bin Wang, Qi-Xiang Lin, Lin Lu, Ni Shu, Shi-Qiu Meng, Jun Wang, Hong-Bin Han, Yong He and Jie Shi

      Article first published online: 16 JUL 2015 | DOI: 10.1111/adb.12285

    9. Is the Internet gaming-addicted brain close to be in a pathological state?

      Chang-hyun Park, Ji-Won Chun, Huyn Cho, Young-Chul Jung, Jihye Choi and Dai Jin Kim

      Article first published online: 1 JUL 2015 | DOI: 10.1111/adb.12282

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      We applied a graph-theoretical approach to analyzing resting state fMRI data in Internet gaming addicted adolescents. Internet gaming addiction induced brain functional networks to shift towards the random topological architecture, which suggested that the Internet gaming addicted brain could be in the state similar to pathological states. The topological alterations were specifically attributable to interregional connections incident on the frontal region, and the degree of impulsiveness was associated with the topological alterations over the frontolimbic connections.

    10. Kv7 channels in the nucleus accumbens are altered by chronic drinking and are targets for reducing alcohol consumption

      Natalie S. McGuier, William C. Griffin III, Justin T. Gass, Audrey E. Padula, Elissa J. Chesler and Patrick J. Mulholland

      Article first published online: 23 JUN 2015 | DOI: 10.1111/adb.12279

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      Using bioinformatics and pharmacological approaches, we found that the genes that encode Kv7 channels (Kcnq2/3) strongly associate with alcohol intake, and positive modulation of Kv7 channels reduced consumption in heavy drinking rats. Long-term drinking also enhanced the sensitivity to the proconvulsant effects of Kv7 channel antagonism and shifted surface trafficking of Kv7.2 channels in the nucleus accumbens core. Finally, we identified 12 possible SUMOylation modification sites on human and rat Kv7.2 and showed that chronic drinking decreased Kv7.2 SUMOylation levels.

    11. Acquisition of morphine conditioned place preference increases the dendritic complexity of nucleus accumbens core neurons

      Kendra L. Kobrin, Olivia Moody, Danielle T. Arena, Catherine F. Moore, Stephen C. Heinrichs and Gary B. Kaplan

      Article first published online: 19 JUN 2015 | DOI: 10.1111/adb.12273

    12. Real-time functional magnetic resonance imaging neurofeedback can reduce striatal cue-reactivity to alcohol stimuli

      Martina Kirsch, Isabella Gruber, Matthias Ruf, Falk Kiefer and Peter Kirsch

      Article first published online: 10 JUN 2015 | DOI: 10.1111/adb.12278

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      Increased activation of the ventral striatum (VS) to alcohol cues has been proposed as neurobiological basis of craving. We tested whether real-time fMRI neurofeedback can modulate cue reactivity. Heavy drinkers were assigned to a real neurofedback group (rFB), a yoke neurofeedback group (yFB) and a passive control group. The rFB group received feedback from their own, the yFB from another participants VS. Both groups were instructed to downregulate the activation. We found VS downregulation specifically for rFB demonstrating the suitability of neurofeedback in alcoholism.

    13. You have full text access to this OnlineOpen article
      Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking

      Petra Suchankova, Staffan Nilsson, Bettina von der Pahlen, Pekka Santtila, Kenneth Sandnabba, Ada Johansson, Patrick Jern, Jörgen A. Engel and Elisabet Jerlhag

      Article first published online: 9 JUN 2015 | DOI: 10.1111/adb.12277

  6. Commentary

  7. Original Articles

    1. Comparison of striatal dopamine transporter levels in chronic heroin-dependent and methamphetamine-dependent subjects

      Jie Yuan, Xing Dang Liu, Mei Han, Rong Bin Lv, Yuan Kai Wang, Guang Ming Zhang and Yu Li

      Article first published online: 4 JUN 2015 | DOI: 10.1111/adb.12271

    2. Model-free functional connectivity and impulsivity correlates of alcohol dependence: a resting-state study

      Xi Zhu, Carlos R. Cortes, Karan Mathur, Dardo Tomasi and Reza Momenan

      Article first published online: 3 JUN 2015 | DOI: 10.1111/adb.12272

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      We investigated the resting state functional connectivity (FC) in alcohol dependent patients (ADs) and examined its relationship with clinical impulsivity measures. ADs exhibited increased within-network FC in salience (SN), default-mode (DMN), orbitofrontal cortex (OFCN), left executive control (LECN) and amygdala-striatum (ASN) networks. Increased between-network FC was found among LECN, ASN and SN. Between-network FC correlations with impulsivity measures were also found in ADs. These findings add evidence to the concept of altered FC in the pathophysiology of ADs.

    3. Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation

      Desirée B. Spronk, Ellen R. A. De Bruijn, Janelle H. P. van Wel, Johannes G. Ramaekers and Robbert J. Verkes

      Article first published online: 3 JUN 2015 | DOI: 10.1111/adb.12274

    4. Role of the satiety factor oleoylethanolamide in alcoholism

      Ainhoa Bilbao, Antonia Serrano, Andrea Cippitelli, Francisco J. Pavón, Andrea Giuffrida, Juan Suárez, Nuria García-Marchena, Elena Baixeras, Raquel Gómez de Heras, Laura Orio, Francisco Alén, Roberto Ciccocioppo, Benjamin F. Cravatt, Loren H. Parsons, Daniele Piomelli and Fernando Rodríguez de Fonseca

      Article first published online: 2 JUN 2015 | DOI: 10.1111/adb.12276

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      Oleoylethanolamide (OEA) is a satiety factor that binds to the peroxisome proliferator-activated receptor-alpha (PPARα). This bioactive lipid mediator also acts as a homeostatic signal that controls multiple aspects of the physiological adaptations to alcohol exposure. OEA production is triggered by alcohol administration, contributes to the regulation of alcohol consumption and the acute motivational response to alcohol, and reduces the severity of somatic withdrawal symptoms.

    5. Role of the α1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial

      George A. Kenna, Carolina L. Haass-Koffler, William H. Zywiak, Steven M. Edwards, Michael B. Brickley, Robert M. Swift and Lorenzo Leggio

      Article first published online: 2 JUN 2015 | DOI: 10.1111/adb.12275

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      The α1 blocker doxazosin was tested in alcoholic patients. Drinks per week (DPW) and heavy drinking days (HDD) per week were the primary outcomes. While there was no main medication effect, when family history density of alcoholism (FHDA) was analyzed as a priori moderator, doxazosin significantly reduced DPW and HDD in patients with high FHDA and by contrast tended to increase drinking in those with low FHDA. This study provides preliminary evidence for personalized medicine using α1-blockade to treat alcoholism.

    6. (R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake

      María Elena Quintanilla, Mario Rivera-Meza, Pablo Berríos-Cárcamo, Bruce K. Cassels, Mario Herrera-Marschitz and Yedy Israel

      Article first published online: 29 MAY 2015 | DOI: 10.1111/adb.12268

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      Ethanol is oxidized in the brain to acetaldehyde, which can condense with dopamine to generate (R/S)-salsolinol [(RS)-SAL]. Behavioral studies in rats have suggested that (RS)-SAL would be involved in the rewarding/reinforcing effects of ethanol. However, it is not known whether the (RS)-SAL effects are due to one or both enantiomers. The present study shows that (R)-salsolinol [(R)-SAL] injected into the ventral tegmental area (VTA) (at days 1, 3, 5 and 13; arrows) greatly produces binge-like ethanol drinking (reaching 3 g ethanol intake/kg/60 minutes) in ethanol-naïve rats. Conversely, (S)-SAL was fully inactive in the same model. Also, administration of (R)-SAL, but not of (S)-SAL, results in conditioned place preference and marked behavioral (locomotor) sensitization. The present studies suggest that (R)-SAL generates long-lasting effects akin to those that have been reported following chronic ethanol intake, and might be considered a mediator of ethanol effects.

    7. Hedonic sensitivity to natural rewards is affected by prenatal stress in a sex-dependent manner

      Marie-Line Reynaert, Jordan Marrocco, Jérôme Mairesse, Luana Lionetto, Maurizio Simmaco, Lucie Deruyter, Delphine Allorge, Anna Moles, Anna Pittaluga, Stefania Maccari, Sara Morley-Fletcher, Gilles Van Camp and Ferdinando Nicoletti

      Article first published online: 26 MAY 2015 | DOI: 10.1111/adb.12270

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      We report that prenatal restraint stress enhances the rewarding properties of a natural reward in male rats, while exerting an opposite effect in females. Changes in hedonic sensitivity to milk chocolate are tightly dependent on changes in gonadal hormones (dihydrotestosterone in males, estradiol in females). Physiological or pharmacological modifications of the hormonal status affect sensitivity to palatable food and related changes in neurobiological substrates: dopamine in the nucleus accumbens of males and serotonin in the prefrontal cortex of females.

  8. Invited Reviews

  9. Original Articles

    1. Lower gray matter density and functional connectivity in the anterior insula in smokers compared with never smokers

      Luke E. Stoeckel, Xiaoqian J. Chai, Jiahe Zhang, Susan Whitfield-Gabrieli and A. Eden Evins

      Article first published online: 20 MAY 2015 | DOI: 10.1111/adb.12262

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      Nicotine addiction is characterized by abnormalities in brain networks involved in salience (anterior insula), semantic processing / emotion regulation (lateral temporal cortex), and cognitive control (lateral prefrontal cortex). Compared to never-smokers, smokers had lower grey matter density in left anterior insula extending into inferior frontal and temporal cortices. Grey matter density was also inversely correlated with cigarettes smoked per day. Smokers also exhibited negative functional connectivity between the anterior insula and left lateral prefrontal and temporal cortices, whereas controls exhibited positive connectivity between these regions.

    2. Increased vulnerability to ethanol consumption in adolescent maternal separated mice

      María S. García-Gutiérrez, Francisco Navarrete, Auxiliadora Aracil, Adrián Bartoll, Isabel Martínez-Gras, José L. Lanciego, Gabriel Rubio and Jorge Manzanares

      Article first published online: 18 MAY 2015 | DOI: 10.1111/adb.12266

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      This study evaluated for the first time the effects of maternal separation with or without additional exposure to other stressful stimuli during adolescence in the consumption, motivation and reinforcing properties of ethanol using the oral ethanol self-administration paradigm. Adolescent MS mice presented higher motivation (increased number of effective response in the active lever) and consumption of ethanol. Interestingly, re-exposure to stressful-like stimuli during adolescence significantly increased the vulnerability to ethanol consumption in MS mice. These results point to the fact that early-life stress increases the vulnerability to later-life stress.

    3. Magnetic resonance imaging structural alterations in brain of alcohol abusers and its association with impulsivity

      Samuel Asensio, Julia L. Morales, Isabel Senabre, Maria J. Romero, Miguel A. Beltran, Miguel Flores-Bellver, Jorge M. Barcia and Francisco J. Romero

      Article first published online: 18 MAY 2015 | DOI: 10.1111/adb.12257

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      Twenty-four patients meeting DSM-IV criteria for alcohol abuse completed the Barratt Impulsiveness Scale and MRI scans were performed for voxel-based morphometry. Lower medial prefrontal cortex (mPFC) grey matter regional volume is correlated with higher impulsivity scores in alcoholic patients. A lower white matter (WM) regional volume underlying mPFC and Orbitofrontal cortex is also found in alcoholic patients. Interestingly, an increased WM volume is found at telencephalic fascicles of ventral striatum. These results give morpho-functional support to the chatracteristic lack of of control over emotional and compulsive behaviors described in these patients.

    4. Lateral hypothalamic melanocortin receptor signaling modulates binge-like ethanol drinking in C57BL/6J mice

      Gretchen M. Sprow, Jennifer A. Rinker, Emily G. Lowery-Gointa, Angela M. Sparrow, Montserrat Navarro and Todd E. Thiele

      Article first published online: 15 MAY 2015 | DOI: 10.1111/adb.12264

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      The present report examined how binge-like ethanol drinking impacts key peptides within the central melanocortin (MC) system. Results showed decreased α-MSH expression and increased agouti-related protein (AgRP) expression within specific hypothalamic sub-regions following repeated binge-like ethanol drinking in male C57BL/6J mice. Consistently, a non-selective MCR agonist (MTII) blunted, while a non-selective MCR antagonist (AgRP) augmented, binge-like ethanol consumption when delivered into the lateral hypothalamus. The present results show that MC signaling within the hypothalamus modulates binge-like ethanol drinking in mice.


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