Addiction Biology

Cover image for Vol. 22 Issue 3

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

Edited By: Rainer Spanagel

Impact Factor: 4.603

ISI Journal Citation Reports © Ranking: 2016: 3/18 (Substance Abuse); 59/286 (Biochemistry & Molecular Biology)

Online ISSN: 1369-1600

Associated Title(s): Addiction


  1. 1 - 100
  2. 101 - 144
  1. Special Issues

    1. CB1 and ethanol effects on glutamatergic transmission in the central amygdala of male and female msP and Wistar rats

      Dean Kirson, Christopher Shaun Oleata, Loren Howell Parsons, Roberto Ciccocioppo and Marisa Roberto

      Version of Record online: 28 JUN 2017 | DOI: 10.1111/adb.12525

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      The Marchigian Sardinian alcohol-preferring (msP) rat simulates the high-stress alcohol-dependent phenotype. We examined cannabinoid receptor type 1 (CB1)-mediated effects on evoked glutamatergic signaling in the central amygdala (CeA), and interactions with acute ethanol, in male and female msP and Wistar rats. We found strain-dependent/sex-dependent inhibition of excitatory postsynaptic potentials with ethanol and CB1 agonism and strain-specific effects of the combined drugs in female rats. These observations demonstrate sex differences in response to the intersection of stress and alcohol.

  2. Original Articles

    1. Long-term subregion-specific encoding of enhanced ethanol intake by D1DR medium spiny neurons of the nucleus accumbens

      Rafael Renteria, Tavanna R. Buske and Richard A. Morrisett

      Version of Record online: 28 JUN 2017 | DOI: 10.1111/adb.12526

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      Using a model of alcohol dependence, chronic intermittent ethanol (CIE), we observed a long-term disruption in the expression of NMDAR-dependent plasticity and a change in the rectification index of AMPA receptor mediated currents in D1 medium spiny neurons (MSNs) of the NAc shell but not the NAc core. These changes in plasticity and excitatory signaling in D1 MSNs of the NAc shell may constitute a critical neuroadaptive response underlying the escalation of ethanol intake in the CIE model.

    2. Noradrenergic signaling in the VTA modulates cocaine craving

      Wojciech Barnaba Solecki, Klaudia Szklarczyk, Kamil Pradel, Krystyna Kwiatkowska, Grzegorz Dobrzański and Ryszard Przewłocki

      Version of Record online: 21 JUN 2017 | DOI: 10.1111/adb.12514

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      Cocaine seeking under extinctiong criteria in rats is attenuated by intra-ventral tegmental area (VTA) selective α1-AR antagonists (prazosin and terazois). In contrast, cocaine seeking is facilitated by intra-VTA administration of the selective α1-AR agonist (phenylephrine) as well as α2-AR antagonist (RX 821002), whereas the selective β-AR antagonist (propranolol) has no effects. Importantly, the potential nonspecific effects of the VTA AR blockade on cocaine seeking could be excluded, because none of the AR antagonists influenced sucrose seeking or locomotor activity.

    3. Novel role and regulation of HDAC4 in cocaine-related behaviors

      Rachel D. Penrod, Maria B. Carreira, Makoto Taniguchi, Jaswinder Kumar, Stephanie A. Maddox and Christopher W. Cowan

      Version of Record online: 21 JUN 2017 | DOI: 10.1111/adb.12522

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      In the nucleus accumbens, HDAC4 is hyperphosphorylated and re-localized to the cytoplasm in response to cocaine. Loss of neuronal HDAC4 in the adult mouse nucleus accumbens reduces behavioral responses to cocaine. Overexpression of a phospho-mimetic mutant of HDAC4 enhances cocaine reward behavior, suggesting a possible cytoplasmic role in addiction-related behaviors.

    4. Locomotor sensitization is expressed by ghrelin and D1 dopamine receptor agonist in the nucleus accumbens core in amphetamine pre-exposed rat

      Ju Kyong Jang, Wha Young Kim, Bo Ram Cho, Jung Won Lee and Jeong-Hoon Kim

      Version of Record online: 21 JUN 2017 | DOI: 10.1111/adb.12533

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      Ghrelin modulates mesolimbic dopaminergic pathways in the brain in addition to its role in feeding. Here, we showed that ghrelin in the nucleus accumbens core significantly enhanced acute amphetamine-induced locomotor activity. Further, ghrelin when co-microinjected into this site with SKF 81297 produced sensitized locomotor activity in amphetamine pre-exposed rats. These results suggest that ghrelin has a distinct role in the nucleus accumbens core to provoke the sensitized locomotor activity induced by psychomotor stimulants, with the help of D1 dopamine receptors.

    5. Buprenorphine requires concomitant activation of NOP and MOP receptors to reduce cocaine consumption

      Marsida Kallupi, Qianwei Shen, Giordano de Guglielmo, Dennis Yasuda, V. Blair Journigan, Nurulain T. Zaveri and Roberto Ciccocioppo

      Version of Record online: 21 JUN 2017 | DOI: 10.1111/adb.12513

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      Buprenorphine, at all doses tested, reduced significantly, in a dose-dependent manner, the number of cocaine rewards. However, treatment with the combination (SB-612111 30.0 mg + Nltx 2.5 mg) completely prevented the reduction of cocaine self-administration by buprenorphine.

    6. Regional cerebral blood flow in opiate dependence relates to substance use and neuropsychological performance

      Donna E. Murray, Timothy C. Durazzo, Thomas P. Schmidt, Troy A. Murray, Christoph Abé, Joseph Guydish and Dieter J. Meyerhoff

      Version of Record online: 19 JUN 2017 | DOI: 10.1111/adb.12523

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      Regional brain perfusion in opiate dependent individuals (sODI) was measured with arterial spin labeling magnetic resonance imaging. Perfusion was increased in anterior cingulate cortex and globus pallidus of sODI. sODI had greater age-related declines in perfusion in most brain reward/executive oversight system regions than control groups (smokers and non-smokers) and a substance-dependent control group. In sODI, lower regional perfusion was related to greater substance use, higher impulsivity, and weaker visuospatial skills. Overall, sODI showed cortical and subcortical hypo-perfusion and hyperperfusion.

    7. Dentate gyrus neurogenesis ablation via cranial irradiation enhances morphine self-administration and locomotor sensitization

      Sarah E. Bulin, Matthew L. Mendoza, Devon R. Richardson, Kwang H. Song, Timothy D. Solberg, Sanghee Yun and Amelia J. Eisch

      Version of Record online: 19 JUN 2017 | DOI: 10.1111/adb.12524

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      Rats underwent hippocampal-focused, image-guided X-ray irradiation to eliminate new dentate gyrus neurons or received a control treatment. Irradiated rats self-administered ˜70% more morphine than control rats, and pressed the active lever ˜40% more than control rats during extinction. Irradiated rats also sensitized faster and to a greater extent than control rats in locomotor sensitization.

    8. Temporally specific miRNA expression patterns in the dorsal and ventral striatum of addiction-prone rats

      Rikki K. Quinn, Morgan H. James, Guy E. Hawkins, Amanda L. Brown, Andrew Heathcote, Doug W. Smith, Murray J. Cairns and Christopher V. Dayas

      Version of Record online: 13 JUN 2017 | DOI: 10.1111/adb.12520

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      Bayesian model averaging (BMA) is a novel method to identify rats with a predisposition to addiction and relapse vulnerability using early behaviour traits. Using our BMA model, we have shown that addiction-prone rats show a distinct temporal profile in miRNA expression in the striatum compared to addiction-resistant rats. Here we show that key miRNA involved in synaptic plasticity processes, including miR-137, and those previously implicated in addiction behaviours, including miR-212, are dysregulated throughout the addiction cycle.

    9. Effect of N-acetylcysteine on motivation, seeking and relapse to ethanol self-administration

      Sophie Lebourgeois, María Carmen González-Marín, Jerome Jeanblanc, Mickael Naassila and Catherine Vilpoux

      Version of Record online: 30 MAY 2017 | DOI: 10.1111/adb.12521

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      We report here N-acetylcysteine (NAC) efficacy to reduce operant ethanol self-administration in rats during short-time session of 15 minutes. NAC also reduces seeking and reacquisition following protracted abstinence. Our results suggest for the first time that NAC is a potential new anticraving treatment for reduction of alcohol relapse.

    10. Effects of sleep on substance use in adolescents: a longitudinal perspective

      Tam T. Nguyen-Louie, Ty Brumback, Matthew J. Worley, Ian M. Colrain, Georg E. Matt, Lindsay M. Squeglia and Susan F. Tapert

      Version of Record online: 26 MAY 2017 | DOI: 10.1111/adb.12519

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      Early–mid adolescent psychiatric health and sleep behaviors prior to drinking onset predicted greater alcohol, marijuana, and tobacco use 5 years later. Erratic sleep/wake behavior was a significant mediator in the effect of baseline inhibition control on lifetime substance use events at follow-up. Participants were substance-naïve at baseline, allowing for the examination of temporal order in the relationship between sleep problems and alcohol use.

    11. Nicotine self-administration reverses cognitive deficits in a rat model for schizophrenia

      Uta Waterhouse, Katharine A. Brennan and Bart A. Ellenbroek

      Version of Record online: 12 MAY 2017 | DOI: 10.1111/adb.12517

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      Prenatal lipopolysaccharide (LPS) induces cognitive deficits in male offspring. Prenatal LPS does not enhance reinforcing properties of nicotine. Nicotine reverses cognitive deficits induced by prenatal LPS treatment.

    12. Altered interhemispheric resting-state functional connectivity in young male smokers

      Dahua Yu, Kai Yuan, Yanzhi Bi, Lin Luo, Jinquan Zhai, Bo Liu, Yangding Li, Jiadong Cheng, Yanyan Guan, Ting Xue, Limei Bu, Shaoping Su, Yao Ma, Wei Qin, Jie Tian and Xiaoqi Lu

      Version of Record online: 5 MAY 2017 | DOI: 10.1111/adb.12515

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      Compared with healthy male non-smokers, young male smokers showed decreased voxel mirrored homotopic voxel (VMHC) values in the insula and putamen, and increased VMHC values in the prefrontal cortex. Correlation analysis demonstrated that there were significant correlations between pack-years and the average VMHC values of the prefrontal cortex and insula. Our results revealed the disrupted homotopic resting-state functional connectivity in young male smokers, which may extend our understanding of smoking.

    13. Dopamine D1 or D2 receptor-expressing neurons in the central nervous system

      Xiaoyan Wei, Tengfei Ma, Yifeng Cheng, Cathy C.Y. Huang, Xuehua Wang, Jiayi Lu and Jun Wang

      Version of Record online: 24 APR 2017 | DOI: 10.1111/adb.12512

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      D1(D2)-GFP and D1(D2)-Cre mice target the same populations of striatal neurons. D1R-expressing and D2R-expressing neurons are highly segregated in the cortex, hippocampus, and amygdala. Excessive alcohol consumption distinctly regulates excitability of D1R-expressing and D2R-expressing ventral CA1 neurons.

    14. Levodopa prevents the reinstatement of cocaine self-administration in rats via potentiation of dopamine release in the medial prefrontal cortex

      Silvia Antinori, Liana Fattore, Pierluigi Saba, Walter Fratta, Gian Luigi Gessa and Paola Devoto

      Version of Record online: 21 APR 2017 | DOI: 10.1111/adb.12509

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      Systemic administration of levodopa (L-DOPA) potentiates cocaine-induced dopamine (DA) release in the rat medial prefrontal cortex (mPFC) during cocaine self-administration and contextually reduces cocaine-taking behavior. In the same brain area, after extinction of self-administration, L-DOPA administration increases DA levels and inhibits cocaine-seeking behavior during cue priming-induced reinstatement. Its ability to prevent cue priming-induced reinstatement of cocaine-seeking suggests that it might be effective in reducing the risk to relapse to cocaine in abstinent patients.

    15. Intravenous self-administration of benzydamine, a non-steroidal anti-inflammatory drug with a central cannabinoidergic mechanism of action

      Riccardo Avvisati, Maria Meringolo, Emiliana Stendardo, Elisa Malavasi, Silvia Marinelli and Aldo Badiani

      Version of Record online: 21 APR 2017 | DOI: 10.1111/adb.12516

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      Abuse of the anti-inflammatory drug benzydamine (BZY) has been reported, especially in drug addicts, but experimental evidence is lacking. We report here that BZY (1) has powerful reinforcing effects in the rat and these effects are facilitated by previous exposure to cocaine and heroin and (2) induces long-term depression of cortico-accumbens synaptic transmission, a phenomenon partially blocked by CB1 receptor antagonism. Our findings provide firm evidence of the addictive potential of BZY and suggest a cannabinoidergic mechanism of action.

    16. Pooled analysis of three randomized, double-blind, placebo controlled trials with rimonabant for smoking cessation

      Jason D. Robinson, Paul M. Cinciripini, Maher Karam-Hage, Henri-Jean Aubin, Lowell C. Dale, Raymond Niaura, Robert M. Anthenelli and the STRATUS Group

      Version of Record online: 21 APR 2017 | DOI: 10.1111/adb.12508

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      We conducted pooled analysis of three previously unpublished trials (STRATUS EU, US, and META) assessing 10 weeks on the CB1 antagonist rimonabant 20 and 5 mg or placebo for smoking cessation. Rimonabant 20 mg resulted in significantly higher abstinence than the 5 mg or placebo dose but also produced increased nausea, diarrhea, anxiety symptoms, hyporexia, and vomiting, and decreased headache, constipation, and cough, compared with placebo. These results may inform and spur the development of other endocannabinoids for smoking cessation.

    17. Nicotine-induced molecular alterations are modulated by GABAB receptor activity

      Andres P. Varani, Valeria T. Pedrón, Amira J. Aon, Christian Höcht, Gabriela B. Acosta, Bernhard Bettler and Graciela N. Balerio

      Version of Record online: 17 APR 2017 | DOI: 10.1111/adb.12506

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      Nicotine induced rewarding effects in the conditioned place preference paradigm and increased dopamine levels in Acb and PFC, α4β2nAChRs density in VTA and c-Fos expression in Acb shell, VTA and PFC. Baclofen prevented the behavioral, neurochemical, biochemical and molecular alterations induced by NIC. However, in saclofen pretreated and GABAB1KO mice, these alterations were potentiated. These results suggest that GABAB receptor activity is necessary to control alterations induced by NIC-induced rewarding effects.

    18. Suvorexant, an orexin/hypocretin receptor antagonist, attenuates motivational and hedonic properties of cocaine

      Taylor A. Gentile, Steven J. Simmons, David J. Barker, Jessica K. Shaw, Rodrigo A. España and John W. Muschamp

      Version of Record online: 17 APR 2017 | DOI: 10.1111/adb.12507

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      Our experiments found that suvorexant, the first-in-class clinically available dual hypocretin/receptor antagonist, reduces cocaine-seeking motivation in rats. Additionally, suvorexant was found to augment hedonic reactivity to systemically injected cocaine and attenuate cocaine-elicited elevations in ventral striatal dopamine release. Collectively, these findings contribute to developing literature positioning hypocretin/orexin receptor antagonists as possible adjunct therapies for treating substance use disorders in humans.

    19. You have full text access to this OnlineOpen article
      A paradigm for examining stress effects on alcohol-motivated behaviors in participants with alcohol use disorder

      Mary E. McCaul, Gary S. Wand, Elise M. Weerts and Xiaoqiang Xu

      Version of Record online: 17 APR 2017 | DOI: 10.1111/adb.12511

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      This study developed an alcohol-motivated response (AMR) procedure to examine effects of psychosocial stress on alcohol craving and several operant behaviors in persons with alcohol use disorder. Following the Trier Psychosocial Stress Test, there was a positive relationship between alcohol craving and drinks earned during the AMR session. This novel paradigm provides an experimental platform to examine motivation to drink without confounding by actual alcohol ingestion during the work session, setting the stage for future studies of alcohol interventions.

    20. You have full text access to this OnlineOpen article
      The involuntary nature of binge drinking: goal directedness and awareness of intention

      Nuria Doñamayor, Daniela Strelchuk, Kwangyeol Baek, Paula Banca and Valerie Voon

      Version of Record online: 16 APR 2017 | DOI: 10.1111/adb.12505

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      Model-based/goal-directed and model-free/habitual behaviours and intention awareness were assessed in 31 severe binge drinkers and 35 healthy volunteers. Binge drinkers showed impaired goal-directed behaviour and delayed intention awareness. Further, alcohol use severity correlated with decreased intention awareness, and the time elapsed since the last drinking binge influenced goal-directed and habitual behaviours. This modulation suggests a state effect of alcohol use in these measures and that top-down volitional control might be ameliorated with alcohol use cessation.

    21. Adolescents' behavioral and neural responses to e-cigarette advertising

      Yvonnes Chen, Carina H. Fowler, Vlad B. Papa, Rebecca J. Lepping, Morgan G. Brucks, Andrew T. Fox and Laura E. Martin

      Version of Record online: 11 APR 2017 | DOI: 10.1111/adb.12510

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      Adolescents (n = 30) with various smoking experiences (non-smokers to daily smokers) self-reported that viewing the e-cigarette advertisements increased their desire to smoke. They also showed significantly greater brain activation to e-cigarette advertisements in areas associated with cognitive control, reward, visual processing/attention, and memory. Further, an exploratory analysis showed that compared to age-matched non-smokers (n = 7), adolescent smokers (n = 7) displayed significantly greater neural activation to e-cigarette advertising images in the left inferior temporal gyrus/fusiform gyrus, compared to their responses to neutral advertising images.

    22. Intra-prelimbic cortical inhibition of striatal-enriched tyrosine phosphatase suppresses cocaine seeking in rats

      Ben M. Siemsen, Paul J. Lombroso and Jacqueline F. McGinty

      Version of Record online: 28 MAR 2017 | DOI: 10.1111/adb.12504

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      Intra-prelimbic cortical inhibition of striatal-enriched protein tyrosine phosphatase with the relatively selective inhibitor, TC-2153, immediately following cocaine self-administration prevents the critical extracellular signal-regulated kinase dephosphorylation within the prelimbic cortex during early abstinence and also prevents subsequent relapse to cocaine seeking following abstinence and extinction training.

    23. Acupuncture reduces relapse to cocaine-seeking behavior via activation of GABA neurons in the ventral tegmental area

      Wyju Jin, Min Sun Kim, Eun Young Jang, Jun Yeon Lee, Jin Gyeom Lee, Hong Yu Kim, Seong Shoon Yoon, Bong Hyo Lee, Suchan Chang, Jae Hyo Kim, Kwang H. Choi, Ho Koo, Young Seob Gwak, Scott C. Steffensen, Yeon-Hee Ryu, Hee Young Kim and Chae Ha Yang

      Version of Record online: 7 MAR 2017 | DOI: 10.1111/adb.12499

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      We provide Figure b as a suitable figure. We also summarized 3 sentences from our findings.

      1. HT7 acupuncture significantly reduced cocaine suppression of γ-aminobutyric acid (GABA) release and GABA neuron firing rates in the ventral tegmental area.
      2. HT7 acupuncture attenuated cocaine-primed reinstatement and cocaine-induced sensitization of extracellular dopamine levels in the nucleus accumbens, which are blocked by GABAB receptor antagonist 2-hydroxysaclofen.
      3. HT7 acupuncture reduced both locomotor activity and neuronal activation in the nucleus accumbens induced by acute cocaine in a needle-penetration depth-dependent fashion.
    24. You have full text access to this OnlineOpen article
      Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals

      Laurel S. Morris, Kwangyeol Baek, Roger Tait, Rebecca Elliott, Karen D. Ersche, Remy Flechais, John McGonigle, Anna Murphy, Liam J. Nestor, Csaba Orban, Filippo Passetti, Louise M. Paterson, Ilan Rabiner, Laurence Reed, Dana Smith, John Suckling, Eleanor M. Taylor, Edward T. Bullmore, Anne R. Lingford-Hughes, Bill Deakin, David J. Nutt, Barbara J. Sahakian, Trevor W. Robbins, Valerie Voon and ICCAM Consortium

      Version of Record online: 28 FEB 2017 | DOI: 10.1111/adb.12503

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      Neural network characteristics were assessed in alcohol-dependent and poly-substance-dependent individuals. Both groups displayed disturbed network topology, suggesting clustered and segregated information processing. A single 50-mg dose of naltrexone, an opioid receptor antagonist commonly used as a relapse prevention medication in addiction, normalized the aberrant neural network organization (local efficiency) in alcohol-dependent and not poly-substance-dependent individuals. These findings suggest that the clinical effects of naltrexone in alcohol-dependent individuals might relate to an amelioration of disrupted network topology.

    25. On the relationships in rhesus macaques between chronic ethanol consumption and the brain transcriptome

      Ovidiu D. Iancu, Alexander Colville, Nicole A.R. Walter, Priscila Darakjian, Denesa L. Oberbeck, James B. Daunais, Christina L. Zheng, Robert P. Searles, Shannon K. McWeeney, Kathleen A. Grant and Robert Hitzemann

      Version of Record online: 28 FEB 2017 | DOI: 10.1111/adb.12501

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      Four cohorts of male rhesus monkeys (n = 32) followed a protocol of >12 months of chronic alcohol self-administration. Analyzing the brain transcriptome in amygdala and cortical area 32 via RNA-Seq revealed coexpression and cosplicing networks that are unique to each other and unique to brain region. Specifically, coexpression modules enriched in genes correlated to alcohol intake reveal increased expression of membrane and synaptic genes and decreased expression of translational genes in amygdala.

    26. In vivo structural imaging in rats reveals neuroanatomical correlates of behavioral sub-dimensions of cocaine addiction

      Nazzareno Cannella, Alejandro Cosa-Linan, Elena Büchler, Claudia Falfan-Melgoza, Wolfgang Weber-Fahr and Rainer Spanagel

      Version of Record online: 23 FEB 2017 | DOI: 10.1111/adb.12500

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      Enhanced somatosensory and insular cortex gray matter volume (GMV) predicts perseverance in cocaine seeking. Lower medial prefontal cortex GMV predicts enhanced motivation for cocaine. Lower PAG periaqueductal gray GMV predicts enhanced compulsivity in addicted rats.

    27. Default mode network deactivation to smoking cue relative to food cue predicts treatment outcome in nicotine use disorder

      Claire E. Wilcox, Eric D. Claus, Vince D. Calhoun, Srinivas Rachakonda, Rae A. Littlewood, Jessica Mickey, Pamela B. Arenella, Natalie Goodreau and Kent E. Hutchison

      Version of Record online: 23 FEB 2017 | DOI: 10.1111/adb.12498

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      One hundred forty-three individuals with nicotine use disorder underwent a visual cue task during functional MRI that involved exposure to smoking (Smoke) and food (Food) cue videos, before undergoing treatment (varenicline or placebo). Greater deactivation to Food relative to Smoke was observed in the default mode network, and a less positive Smoke–Food difference score predicted worse treatment outcomes, combining both treatment groups. A more positive Smoke–Food difference score in executive control network predicted a better response to varenicline relative to placebo.

    28. You have full text access to this OnlineOpen article
      Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction

      Gunnar W. Reginsson, Andres Ingason, Jack Euesden, Gyda Bjornsdottir, Sigurgeir Olafsson, Engilbert Sigurdsson, Hogni Oskarsson, Thorarinn Tyrfingsson, Valgerdur Runarsdottir, Ingunn Hansdottir, Stacy Steinberg, Hreinn Stefansson, Daniel F. Gudbjartsson, Thorgeir E. Thorgeirsson and Kari Stefansson

      Version of Record online: 23 FEB 2017 | DOI: 10.1111/adb.12496

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      Using polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking behavior and alcohol or drug addiction in 144,609 subjects, we find that smoking and diagnoses of various substance use disorders associate strongly with PRSs for SCZ (P = 5.3 × 10−50–1.4 × 10−6) and BPD (P = 1.7 × 10−9–1.9 × 10−3). Furthermore, we show that the impact of SCZ-PRS on smoking is rising with time, increasingly casting regular smoking as a psychiatric condition sharing genetic risk with SCZ and BPD.

  3. Commentaries

    1. You have free access to this content
      Addiction research and theory: a commentary on the Surgeon General's Report on alcohol, drugs, and health

      Aldo Badiani, Kent C. Berridge, Markus Heilig, David J. Nutt and Terry E. Robinson

      Version of Record online: 21 FEB 2017 | DOI: 10.1111/adb.12497

  4. Original Articles

    1. Modeling human methamphetamine use patterns in mice: chronic and binge methamphetamine exposure, reward function and neurochemistry

      James P. Kesby, Ariel Chang, Athina Markou and Svetlana Semenova

      Version of Record online: 21 FEB 2017 | DOI: 10.1111/adb.12502

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      We examined human-derived binge and chronic methamphetamine use patterns in mice. Both regimens induced a similar magnitude of reward deficits during withdrawal and methamphetamine-challenge-induced reward enhancement. The binge regimen depleted dopamine levels in the striatum and increased glutamine levels throughout the brain. The chronic regimen moderately decreased dopamine levels in the striatum and altered cortical dopamine and serotonin levels. This study demonstrates that aspects of reward and neurochemistry can be either independent or dependent on methamphetamine use parameters.

    2. Cannabidiol reduces ethanol consumption, motivation and relapse in mice

      Adrián Viudez-Martínez, María S. García-Gutiérrez, Carmen María Navarrón, María Isabel Morales-Calero, Francisco Navarrete, Ana Isabel Torres-Suárez and Jorge Manzanares

      Version of Record online: 13 FEB 2017 | DOI: 10.1111/adb.12495

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      The present study strongly points out that cannabidiol (CBD) reduced the reinforcing and motivational properties of ethanol and prevented ethanol-induced relapse. These behavioral alterations are associated with alterations in key targets closely related with alcohol addiction (Oprm-1, TH, CB1r, CB2r and GPR55). In conclusion, the results suggest that CBD deserves further exploration as a potential therapeutic drug for the treatment of alcohol use disorders (AUD).

    3. Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions

      Sarah W. Yip, Patrick D. Worhunsky, Jiansong Xu, Kristen P. Morie, R. Todd Constable, Robert T. Malison, Kathleen M. Carroll and Marc N. Potenza

      Version of Record online: 1 FEB 2017 | DOI: 10.1111/adb.12492

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      Between-group analyses indicated reduced prefrontal cortical gray matter among individuals with cocaine-use disorder (n = 37) versus individuals with gambling disorder (n = 35) and healthy controls (n = 37). Regression analyses indicated a negative association between trait impulsivity and gray matter within cortical (insula) and subcortical (amygdala and hippocampus) regions across all participants. Conjunction analyses indicated little anatomical overlap between regions identified as differentiating diagnostic groups versus those identified as covarying with impulsivity, raising the possibility of dissociable anatomical substrates of diagnosis and impulsivity in addictions.

    4. Bidirectional relationship between alcohol intake and sensitivity to social defeat: association with Tacr1 and Avp expression

      Britta S. Nelson, Michelle K. Sequeira and Jesse R. Schank

      Version of Record online: 1 FEB 2017 | DOI: 10.1111/adb.12494

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      Although the comorbidity between alcoholism and depression is well established, the degree to which either condition precedes or affects the other is unknown. We used preclinical models to elucidate potential behavioral and molecular interactions between these two conditions. Our findings support a bidirectional relationship, with the onset on one condition increasing the risk of the other as well as identifying NK1R and AVP expression as factors involved in increased susceptibility for depressive and addictive behaviors.

    5. Severity of alcohol dependence is associated with the fatty acid amide hydrolase Pro129Thr missense variant

      Matthew E. Sloan, Joshua L. Gowin, Jia Yan, Melanie L. Schwandt, Primavera A. Spagnolo, Hui Sun, Colin A. Hodgkinson, David Goldman and Vijay A. Ramchandani

      Version of Record online: 1 FEB 2017 | DOI: 10.1111/adb.12491

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      The endocannabinoid system modulates brain reward signaling and is thought to influence addictive behaviors. We investigated whether a functional polymorphism in the fatty acid amide hydrolase (FAAH) gene, which encodes an enzyme responsible for metabolizing the endocannabinoid neurotransmitter anandamide, is associated with both risk and severity of alcohol dependence. European American Thr129 allele carriers had higher odds of a current diagnosis of alcohol dependence compared to non-dependent controls (OR = 1.35, 95% CI 1.05 to 1.74) after controlling for covariates. European American alcohol dependent Thr129 carriers reported a median of 10 fewer abstinence days and 13 more binge drinking days during a 90-day recall period than Pro129/Pro129 homozygotes. These findings suggest that endocannabinoid signaling may play an important role in human alcohol consumption.

    6. Whole genome sequence study of cannabis dependence in two independent cohorts

      Ian R. Gizer, Chris Bizon, David A. Gilder, Cindy L. Ehlers and Kirk C. Wilhelmsen

      Version of Record online: 23 JAN 2017 | DOI: 10.1111/adb.12489

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      The present study used low-coverage whole genome sequence data to conduct set-based association analyses of low frequency variation in protein-coding regions as well as regulatory regions in relation to cannabis dependence. Sequence kernel association tests identified one protein-coding region, C1orf110, and one regulatory region in the MEF2B gene that achieved significance in a meta-analysis of both samples. The MEF2B regulatory element was characterized by H3K9me3 and H3K36me histone marks, suggesting it may be important for protecting exons from recombination and regulation of alternative splicing.

    7. No association of goal-directed and habitual control with alcohol consumption in young adults

      Stephan Nebe, Nils B. Kroemer, Daniel J. Schad, Nadine Bernhardt, Miriam Sebold, Dirk K. Müller, Lucie Scholl, Sören Kuitunen-Paul, Andreas Heinz, Michael A. Rapp, Quentin J.M. Huys and Michael N. Smolka

      Version of Record online: 23 JAN 2017 | DOI: 10.1111/adb.12490

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      There is no association between behavioral control during a sequential decision-making task, and fMRI BOLD correlates thereof with alcohol consumption in 188 young social-drinking adults.

    8. You have full text access to this OnlineOpen article
      Binge drinking differentially affects cortical and subcortical microstructure

      Laurel S. Morris, Nicholas G. Dowell, Mara Cercignani, Neil A. Harrison and Valerie Voon

      Version of Record online: 20 JAN 2017 | DOI: 10.1111/adb.12493

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      Chronic or harmful alcohol use is associated with neuroplastic changes, particularly in regions associated with reward processing and motivation. Binge drinkers demonstrated disturbed neurite complexity in the dorsolateral prefrontal cortex and parietal regions, as measured by Neurite Orientation Dispersion and Density Imaging. Heightened neurite complexity in the ventral striatum of binge drinkers was associated with a more severe binge-like pattern of alcohol consumption. Disturbed microstructure in cortical and subcortical regions may reflect a disruption in higher-order prefrontal control systems and enhanced involvement of reward-related motivational systems.

    9. Biological stress indicators as risk markers for increased alcohol use following traumatic experiences

      Sebastian Trautmann, Markus Muehlhan, Clemens Kirschbaum, Hans-Ulrich Wittchen, Michael Höfler, Tobias Stalder and Susann Steudte-Schmiedgen

      Version of Record online: 20 JAN 2017 | DOI: 10.1111/adb.12487

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      We analyzed the predictive value of basal cortisol secretion [hair cortisol concentrations (HCCs)] and stress reactivity (cortisol and alpha amylase response to a laboratory stressor) for the risk of increased alcohol use following traumatic events. The number of traumatic events was related to subsequent alcohol use only in individuals with low HCC, suggesting HCC as a valuable target for potential risk markers of increased alcohol use following stressful events.

    10. Netrin G1: its downregulation in the nucleus accumbens of cocaine-conditioned mice and genetic association in human cocaine dependence

      Sabah Kelaï, Nicolas Ramoz, Jean-Marie Moalic, Florence Noble, Naguib Mechawar, Sandrine Imbeaud, Gustavo Turecki, Michel Simonneau, Philip Gorwood and Gilles Maussion

      Version of Record online: 11 JAN 2017 | DOI: 10.1111/adb.12485

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      We found a decreased Ntng1 expression in the nucleus accumbens of mice conditioned to cocaine. Furthermore, significant genetic family-based associations were detected between NTNG1 polymorphisms and cocaine dependence in 146 multiplex families of the Collaborative study on Genetics of Alcoholism. The data suggest that change in the NTNG1 expression is a consequence of cocaine exposure, and that some of its genetic markers are associated with a greater risk for cocaine use disorder.

    11. Low distress tolerance predicts heightened drug seeking and taking after extended abstinence from cocaine self-administration

      Travis M. Moschak, Douglas R. Terry, Stacey B. Daughters and Regina M. Carelli

      Version of Record online: 11 JAN 2017 | DOI: 10.1111/adb.12488

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      Distress tolerance (DT), defined as the ability to persist in goal-directed behavior while experiencing distress, is associated with greater frequency of substance use and poor treatment outcomes. We developed a rodent model of DT and found that DT measured after cocaine abstinence significantly predicted subsequent high levels of cocaine seeking/taking and that some of these effects were moderated by impulsivity. Collectively, these results support the validity of our rodent DT model while extending the human literature.

    12. CYP2A6 metabolism in the development of smoking behaviors in young adults

      Emily Olfson, Joseph Bloom, Sarah Bertelsen, John P Budde, Naomi Breslau, Andrew Brooks, Robert Culverhouse, Grace Chan, Li-Shiun Chen, David Chorlian, Danielle M Dick, Howard J Edenberg, Sarah Hartz, Dorothy Hatsukami, Victor M Hesselbrock, Eric O Johnson, John R Kramer, Samuel Kuperman, Jacquelyn L Meyers, John Nurnberger, Bernice Porjesz, Nancy L Saccone, Marc A Schuckit, Jerry Stitzel, Jay A Tischfield, John P Rice, Alison Goate and Laura J Bierut

      Version of Record online: 29 DEC 2016 | DOI: 10.1111/adb.12477

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      This study links variation in a genome-wide significant gene, Cytochrome P450 2A6 (CYP2A6), with smoking behaviors in two independent young adult samples. The results demonstrate that a validated CYP2A6 metabolism metric is not associated with smoking initiation nor the development of daily use, but among young adult daily smokers, slow metabolism is associated with an elevated risk of nicotine dependence, which may be driven by time to first cigarette after waking. These findings elucidate the complex role of CYP2A6 variation in smoking behaviors.

    13. Heavy alcohol use in adolescence is associated with altered cortical activity: a combined TMS–EEG study

      Outi Kaarre, Elisa Kallioniemi, Mervi Könönen, Tommi Tolmunen, Virve Kekkonen, Petri Kivimäki, Noora Heikkinen, Florinda Ferreri, Eila Laukkanen and Sara Määttä

      Version of Record online: 23 DEC 2016 | DOI: 10.1111/adb.12486

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      In this study, 27 young adults with heavy alcohol use in adolescence and 25 controls participated in TMS–EEG measurements. We observed a marked increase in the GABAergic N45 amplitude, as well as significant topographical differences in the P60 and N100 in those with a history of heavy drinking. These findings suggest that long-term alcohol use in adolescence, even when not meeting the diagnostic criteria for a disorder, is associated with changes in connectivity and cortical excitability.

    14. d-Cycloserine enhanced extinction of cocaine-induced conditioned place preference is attenuated in serotonin transporter knockout rats

      Peter Karel, Francesca Calabrese, Marco Riva, Paola Brivio, Bas Van der Veen, Liesbeth Reneman, Michel Verheij and Judith Homberg

      Version of Record online: 12 DEC 2016 | DOI: 10.1111/adb.12483

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      In the past, D-cycloserine (DCS) has been used to enhance extinction retention in laboratory animals. Here, we test if DCS is able to reduce drug seeking behavior in 5-HTT−/− rats after mRNA analysis showed a reduction in relevant NMDA receptor composition. We show that 5-HTT−/− rats need a higher dose of DCS to be able to reduce their drug-seeking behavior.

    15. Smokers and ex-smokers have shared differences in the neural substrates for potential monetary gains and losses

      Liam J. Nestor, Ella McCabe, Jennifer Jones, Luke Clancy and Hugh Garavan

      Version of Record online: 12 DEC 2016 | DOI: 10.1111/adb.12484

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      Ex-smokers and smokers show significantly greater activation changes (*p < 0.05) in the orbitofrontal/insular cortex compared with controls during the anticipation of potential monetary gains. This may represent a heightened motivational drive, and emotional and interoceptive state during non-drug reward expectancy. This effect may arise from the sensitizing effect of nicotine on fronto-striatal circuitry.

    16. Distinct intrinsic functional brain network abnormalities in methamphetamine-dependent patients with and without a history of psychosis

      Jonathan C. Ipser, Anne Uhlmann, Paul Taylor, Brian H. Harvey, Don Wilson and Dan J. Stein

      Version of Record online: 5 DEC 2016 | DOI: 10.1111/adb.12478

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      Abnormal connectivity was observed between intrinsic functional cognitive control networks and task-negative default mode networks in the brains of 19 patients with a history of methamphetamine-associated psychosis. Connectivity approached levels observed in 26 healthy controls with increasing antipsychotic treatment duration. Hyperconnectivity between default mode networks was restricted to 27 methamphetamine-dependent patients without methamphetamine-associated psychosis, “normalizing” with longer abstinence.

    17. Putamen functional connectivity during inhibitory control in smokers and non-smokers

      Sophie E. A. Akkermans, Maartje Luijten, Daan van Rooij, Ingmar H. A. Franken and Jan K. Buitelaar

      Version of Record online: 5 DEC 2016 | DOI: 10.1111/adb.12482

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      This study investigated functional connectivity of the anterior and posterior putamen (specialized in goal-directed and habitual responding, respectively) in 25 smokers and 23 non-smokers who completed a Go–NoGo task. We hypothesized that smokers would show weaker connectivity in the anterior putamen (goal-directed) network and more interference of the posterior putamen (habitual) network during inhibition. Instead, smokers displayed stronger inhibition-related connectivity between the anterior putamen and insula compared with non-smokers, which suggests involvement of putamen–insula interactions in addiction and impulse control.

    18. Comparing rewarding and reinforcing properties between ‘bath salt’ 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using ultrasonic vocalizations in rats

      Steven J. Simmons, Ryan A. Gregg, Fionya H. Tran, Lili Mo, Eva von Weltin, David J. Barker, Taylor A. Gentile, Lucas R. Watterson, Scott M. Rawls and John W. Muschamp

      Version of Record online: 1 DEC 2016 | DOI: 10.1111/adb.12479

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      Our work shows that the synthetic cathinone 3,4-methylenedioxypyrovalerone evokes sustained rewarding effects (assessed via 50-kHz ultrasonic vocalizations) in systemic dose-response and self-administration models compared with cocaine. Results extend growing literature on abuse liability associated with novel psychoactive substances including cathinone analogs. Future work should identify neuronal circuits governing positive subjective effects of 3,4-methylenedioxypyrovalerone that in turn direct drug-seeking behavior.

    19. Craving behavioral intervention for internet gaming disorder: remediation of functional connectivity of the ventral striatum

      Jin-Tao Zhang, Shan-Shan Ma, Chiang-Shan R. Li, Lu Liu, Cui-Cui Xia, Jing Lan, Ling-Jiao Wang, Ben Liu, Yuan-Wei Yao and Xiao-Yi Fang

      Version of Record online: 28 NOV 2016 | DOI: 10.1111/adb.12474

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      Internet gaming disorder subjects showed greater resting-state functional connectivity of ventral striatum to left inferior parietal lobule, right inferior frontal gyrus, and left middle frontal gyrus. The strength of ventral striatum-left inferior parietal lobule connectivity was reduced, along with amelioration in addiction severity following the craving behavioral intervention.

    20. Cue-induced nicotine-seeking behavior after withdrawal with or without extinction in rats

      Athina Markou, Jie Li, Kearny Tse and Xia Li

      Version of Record online: 28 NOV 2016 | DOI: 10.1111/adb.12480

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      The present studies show the profound time-dependent changes in cue-induced nicotine-seeking behavior under different withdrawal conditions in nicotine-experienced rats. Non-reinforced operant responding during cue-induced nicotine seeking after different periods of withdrawal from nicotine exhibited an inverted U-shaped curve, with higher levels of responding after 7–21 days of withdrawal than those after 1-day or 42-day withdrawal.

    21. Impact of alcohol use on EEG dynamics of response inhibition: a cotwin control analysis

      Jeremy Harper, Stephen M. Malone and William G. Iacono

      Version of Record online: 18 NOV 2016 | DOI: 10.1111/adb.12481

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      In a large (N = 300) population-based sample of 24-year-old twins, alcohol use was negatively associated with EEG theta-band medial frontal cortex power and medial-dorsal prefrontal cortex functional connectivity during response inhibition, and this effect was stronger among women. A cotwin analysis suggested that, for women, reduced nogo-related theta-band dynamics were consistent with the potential deleterious causal effects of alcohol exposure.

    22. Low-level alcohol consumption during adolescence and its impact on cognitive control development

      Sarah Jurk, Eva Mennigen, Thomas Goschke and Michael N. Smolka

      Version of Record online: 17 NOV 2016 | DOI: 10.1111/adb.12467

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      Investigating the relationship between the development of cognitive control and alcohol consumption across adolescence, we found that neither behavioural nor neural measures of cognitive control at age 14 predicted alcohol use at age 18. As expected, cognitive control abilities and activation of involved brain networks increased from age 14 to 18. Nevertheless, low-level alcohol consumption did not impair ongoing maturation.

    23. You have full text access to this OnlineOpen article
      Methamphetamine self-administration reduces alcohol consumption and preference in alcohol-preferring P rats

      Madeline C. Winkler, Emilee M. Greager, Jacob Stafford and Ryan K. Bachtell

      Version of Record online: 16 NOV 2016 | DOI: 10.1111/adb.12476

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      Self-administration of methamphetamine in alcohol-preferring P rats disrupts alcohol consumption and preference. These effects are restricted to the period of co-use and do not produce persistent effects beyond the co-use period. Although not depicted in this figure, alcohol consumption does not produce reliable, robust effects on methamphetamine intake.

    24. Characterization of hangover following intravenous alcohol exposure in social drinkers: methodological and clinical implications

      Vatsalya Vatsalya, Bethany L. Stangl, Veronica Y. Schmidt and Vijay A. Ramchandani

      Version of Record online: 11 NOV 2016 | DOI: 10.1111/adb.12469

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      “This study characterized hangover symptoms after IV alcohol in social drinkers. There was a 79% prevalence of hangover following a 0.06 g% alcohol clamp. Females and heavier drinkers reported greater hangover symptoms. Self-reported stimulation and intoxication were also associated with hangover. These findings extend previous research on association of hangover with risk factors for alcohol use disorders including drinking history.”

    25. PPARγ agonism attenuates cocaine cue reactivity

      William R Miller, Robert G Fox, Sonja J Stutz, Scott D Lane, Larry Denner, Kathryn A Cunningham and Kelly T Dineley

      Version of Record online: 11 NOV 2016 | DOI: 10.1111/adb.12471

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      Our previous work discovered that extracellular signal-regulated kinase (ERK) interacts with the nuclear receptor and transcription factor, peroxisome proliferator activated receptor gamma (PPARγ), in a dynamic multiprotein complex that facilitates ERK/CREB/CBP-dependent memory consolidation. Abstinence from cocaine self-administration leads to ERK dysregulation and enhanced cue reactivity. We found that PPARγ agonism attenuates cocaine cue reactivity and normalizes ERK. Thus, PPARγ agonism may counteract cocaine cue reactivity and extend abstinence.

    26. The role of CA3-LS-VTA loop in the formation of conditioned place preference induced by context-associated reward memory for morphine

      Jin-Xiang Jiang, Huan Liu, Zhen-Zhen Huang, Yue Cui, Xue-Qin Zhang, Xiao-Long Zhang, Yu Cui and Wen-Jun Xin

      Version of Record online: 11 NOV 2016 | DOI: 10.1111/adb.12468

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      These results, for the first time, illustrated the involvement of neural circuitry of CA3-LSc-VTA, through integration of the contexts and reward information, participated in the reinstatement of conditioned place preference induced by exposure to morphine-associated context, which advanced our understanding on neurobiological basis for the context-associated memory and rewarding behavior.

    27. Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving

      Ryan M. Glynn, J. Amiel Rosenkranz, Marina E. Wolf, Aaron Caccamise, Freya Shroff, Alyssa B. Smith and Jessica A. Loweth

      Version of Record online: 11 NOV 2016 | DOI: 10.1111/adb.12475

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      During the first month of withdrawal from extended-access cocaine self-administration, cue-induced cocaine seeking progressively intensifies (‘incubates’). We found that repeated restraint stress exposure during the first 2 weeks of withdrawal accelerates this incubation process in adult male rats and may make these animals more susceptible to the relapse-promoting effects of a subsequent stressful episode.

    28. Metabolic alterations in the anterior cingulate cortex and related cognitive deficits in late adolescent methamphetamine users

      Jieun E. Kim, Geon Ha Kim, Jaeuk Hwang, Jung Yoon Kim, Perry F. Renshaw, Deborah A. Yurgelun-Todd, Binna Kim, Ilhyang Kang, Saerom Jeon, Jiyoung Ma, In Kyoon Lyoo and Sujung Yoon

      Version of Record online: 4 NOV 2016 | DOI: 10.1111/adb.12473

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      In this study using proton magnetic resonance spectroscopy, we found that the use of methamphetamine, a highly addictive psychostimulant, during adolescence may be associated with metabolic dysfunction in the anterior cingulate cortex and its related cognitive impairment. Interestingly, the age of exposure is critical for the methamphetamine-induced neurotoxic consequences.

    29. Effects of high-dose ethanol intoxication and hangover on cognitive flexibility

      Nicole Wolff, Philipp Gussek, Ann-Kathrin Stock and Christian Beste

      Version of Record online: 27 OCT 2016 | DOI: 10.1111/adb.12470

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      High dose ethanol intoxication affects switching in conditions that involve working memory processes, while switching without memory load remains unaffected. These modulations are accompanied by corresponding effects in the anterior cingulate cortex. During states of sober and hangover, no differences were observed, suggesting that the results seem unlikely to be explained via the dopaminergic system but via the gamma aminobutyric acid system.

    30. The new designer drug buphedrone produces rewarding properties via dopamine D1 receptor activation

      Ji-Hwan Oh, Ji-Young Hwang, Sa-Ik Hong, Shi-Xun Ma, Jee-Yeon Seo, Seok-Yong Lee, Hyoung-Chun Kim and Choon-Gon Jang

      Version of Record online: 27 OCT 2016 | DOI: 10.1111/adb.12472

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      Substituted cathinones are widely abused worldwide. In this study, buphedrone, a type of cathinone, increased conditioned place preference, self-administration, locomotor activity, and induced behavioral sensitization. The rewarding property of buphedrone may be through dopamine D1 receptor activation.

    31. A clinical trial with combined transcranial direct current stimulation and alcohol approach bias retraining

      Tess E. den Uyl, Thomas E. Gladwin, Mike Rinck, Johannes Lindenmeyer and Reinout W. Wiers

      Version of Record online: 27 OCT 2016 | DOI: 10.1111/adb.12463

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      This study investigated whether 2 mA of transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex could enhance effects of four sessions of cognitive bias modification (CBM). No strong evidence for a specific enhancement effect of tDCS on CBM was found. In a post-hoc analysis, tDCS combined with CBM did show a promising trend on treatment outcome.

    32. Increase of KCC2 in hippocampal synaptic plasticity disturbances after perinatal ethanol exposure

      Benoît Silvestre de Ferron, Catherine Vilpoux, Myriam Kervern, Alexandre Robert, Johan Antol, Mickael Naassila and Olivier Pierrefiche

      Version of Record online: 25 OCT 2016 | DOI: 10.1111/adb.12465

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      In rat CA1 pyramidal cell, ethanol exposure during brain development disturbs long-term synaptic plasticity via an increase in the role of KCC2 co-transporter. Bumetanide, a dose-dependent blocker of the two chloride cotransporters NKCC1 and KCC2 help restoring new equilibrium between the roles of these transporters.

    33. Region specific activation of the AKT and mTORC1 pathway in response to excessive alcohol intake in rodents

      Sophie Laguesse, Nadege Morisot, Khanhky Phamluong and Dorit Ron

      Version of Record online: 20 OCT 2016 | DOI: 10.1111/adb.12464

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      Excessive alcohol intake, but not moderate alcohol or sucrose consumption, produces a brain region selective activation of the AKT/mTORC1 pathway in the nucleus accumbens shell and the orbitofrontal cortex of rodents, which is likely to contribute to local molecular mechanisms that underlie the development and maintenance of alcohol drinking behavior.

    34. You have full text access to this OnlineOpen article
      Evidence for GABA-A receptor dysregulation in gambling disorder: correlation with impulsivity

      Inge Mick, Anna C. Ramos, Jim Myers, Paul R. Stokes, Samantha Chandrasekera, David Erritzoe, Maria A. Mendez, Roger N. Gunn, Eugenii A. Rabiner, Graham E. Searle, José C. F. Galduróz, Adam D. Waldman, Henrietta Bowden-Jones, Luke Clark, David J. Nutt and Anne R. Lingford-Hughes

      Version of Record online: 13 OCT 2016 | DOI: 10.1111/adb.12457

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      We used [11C]Ro15–4513 PET to assess GABA-a5 receptor availability in gambling disorder (GD) and impulsivity. We found significantly higher [11C]Ro15–4513 total distribution volume (VT) in the right hippocampus in GD compared with healthy volunteers. We found higher levels of The ‘Negative Urgency’ construct of impulsivity in GD that positively associated with higher [11C]Ro15–4513 VT in the amygdala in the GD group; no such significant correlations were evident in the healthy volunteers group.

    35. Progressive white matter impairment as a predictor of outcome in a cohort of opioid-dependent patient's post-detoxification

      Jo-Hanna Ivers, Jacqueline Fitzgerald, Christopher Whelan, Brion Sweeney, Eamon Keenan, Andrew Fagan, Jason McMarrow, Jim Meany, Joe Barry and Thomas Frodl

      Version of Record online: 13 OCT 2016 | DOI: 10.1111/adb.12466

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      • The scale and extent of white matter impairment in opioid-dependent patients may be associated with duration of use.
      • The change between connections in subcortical regions is pronounced in long-term users compared with short-term and medium-term users.
      • The consequence of changes in the subcortical region has serious repercussions for opioid-dependent patients, as the struggle for recovery is, for the most part, a struggle to regulate cognitive and emotional functions.
    36. Cocaine-induced synaptic structural modification is differentially regulated by dopamine D1 and D3 receptors-mediated signaling pathways

      Lei Zhang, Lu Huang, Kangrong Lu, Yutong Liu, Genghong Tu, Mengjuan Zhu, Li Ying, Jinlan Zhao, N. Liu, Fukun Guo, Lin Zhang and Lu Zhang

      Version of Record online: 12 OCT 2016 | DOI: 10.1111/adb.12462

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      By using the unbiased quantitative stereological physical dissector method, we provide direct electron microscopy evidence that dopamine D1 and D3 receptors reciprocally regulate the ultra-structural changes of synapses following chronic exposure to cocaine. In addition, our data suggest that D1 and D3 receptors may regulate cocaine-induced ultra-structural changes and behavior responses by impact on structural plasticity and signaling transduction.

    37. Impairment of opiate-mediated behaviors by the selective TRPV1 antagonist SB366791

      Shi-Xun Ma, Seung-Hwan Kwon, Jee-Yeon Seo, Ji-Young Hwang, Sa-Ik Hong, Hyoung-Chun Kim, Seok-Yong Lee and Choon-Gon Jang

      Version of Record online: 11 OCT 2016 | DOI: 10.1111/adb.12460

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      We found that treatment with a selective TRPV1 antagonist, SB366791, significantly decreased morphine self-administration on a fixed-ratio 1 schedule or a progressive ratio schedule of reinforcement. In addition, treatment with another selective TRPV1 antagonist, AMG9810, not only significantly prevented morphine self-administration but also prevented morphine-induced c-fos expression in the nucleus accumbens. Furthermore, administration of SB366791 decreased an anxiolytic-like effect during the morphine abstinence period. Moreover, treatment with SB366791 significantly decreased morphine-priming reinstatement.

    38. Gender differences in the inflammatory cytokine and chemokine profiles induced by binge ethanol drinking in adolescence

      María Pascual, Jorge Montesinos, Miguel Marcos, Jorge-Luis Torres, Pilar Costa-Alba, Francisco García-García, Francisco-Javier Laso and Consuelo Guerri

      Version of Record online: 4 OCT 2016 | DOI: 10.1111/adb.12461

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      Female adolescents are more vulnerable than male adolescents to the inflammatory effects of binge alcohol drinking. Circulating cytokines and chemokines might serve as clinical biomarkers of neuroinflammation. The TLR4 response is an important target of the ethanol-induced immune and neuroimmune response in adolescence. This figure shows a negative correlation (Pearson's coefficient) between cytokines/chemokines and blood alcohol levels in intoxicated females (red ellipses) and positive correlation in intoxicated males (blue ellipses). Black and white points denote significance and tendency, respectively.

    39. Impaired decision-making and impulse control in Internet gaming addicts: evidence from the comparison with recreational Internet game users

      Yifan Wang, Lingdan Wu, Lingxiao Wang, Yifen Zhang, Xiaoxia Du and Guangheng Dong

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/adb.12458

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      During the delay discounting and probabilistic discounting tasks, the Internet gaming disorder is more impulsive and shows lower brain activation in the parahippocampal gyrus, anterior cingulate cortex, inferior frontal gyrus, and medial frontal gyrus than recreational Internet gaming users. The results suggest that the recreational Internet gaming users are capable to inhibit impulse due to additional cognitive endeavor, and the Internet gaming disorder has deficit indecision-making and impulsive control. The brain regions are involved in decision-making and cognitive control and may be a key mechanism preventing recreational game players from the risk of developing addiction.

    40. Emotional, physical and sexual abuse are associated with a heightened limbic response to cocaine cues

      Paul S. Regier, Zachary A. Monge, Teresa R. Franklin, Reagan R. Wetherill, Anne Teitelman, Kanchana Jagannathan, Jesse J. Suh, Ze Wang, Kimberly A. Young, Michael Gawrysiak, Daniel D. Langleben, Kyle M. Kampman, Charles P. O'Brien and Anna Rose Childress

      Version of Record online: 22 SEP 2016 | DOI: 10.1111/adb.12445

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      Even though all participants had severe cocaine disorders, individuals with a history of emotional, physical, and/or sexual abuse exhibited a heightened mesolimbic response to cocaine cues compared with those without a history of abuse.

    41. A hypo-status in drug-dependent brain revealed by multi-modal MRI

      Ze Wang, Jesse Suh, Dingna Duan, Stefanie Darnley, Ying Jing, Jian Zhang, Charles O'Brien and Anna Rose Childress

      Version of Record online: 22 SEP 2016 | DOI: 10.1111/adb.12459

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      Brain atrophy (hot), hypoperfusion (violet), and hypoentropy (green) patterns in cocaine patients.

    42. Essential values of cocaine and non-drug alternatives predict the choice between them

      David N. Kearns, Jung S. Kim, Brendan J. Tunstall and Alan Silberberg

      Version of Record online: 14 SEP 2016 | DOI: 10.1111/adb.12450

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      Individual differences in how rats valued cocaine or a non-drug alternative (food or saccharin) predicted subsequent choice behavior in an animal model of addiction. Rats that placed either high value on cocaine or low value on the non-drug alternative were most likely to prefer cocaine. These results are consistent with the notion that addiction involves both overvaluation of drug rewards and undervaluation of non-drug alternatives.

    43. White matter integrity between left basal ganglia and left prefrontal cortex is compromised in gambling disorder

      Tim van Timmeren, Jochem M. Jansen, Matthan W. A. Caan, Anna E. Goudriaan and Ruth J. van Holst

      Version of Record online: 9 SEP 2016 | DOI: 10.1111/adb.12447

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      In this multi-modal study, we investigated cognitive flexibility, associated brain activity and white matter integrity in gambling disorder. We found decreased corticostriatal white matter integrity in pathological gamblers in a tract specifically essential for cognitive flexibility. We argue that this may be an underlying risk factor for gambling disorder, which may extend to addiction in general.

    44. Executive control network connectivity strength protects against relapse to cocaine use

      Meredith J. McHugh, Hong Gu, Yihong Yang, Bryon Adinoff and Elliot A. Stein

      Version of Record online: 7 SEP 2016 | DOI: 10.1111/adb.12448

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      Resting state connectivity was examined in 45 individuals immediately prior to discharge from treatment for cocaine dependence. Connectivity strength within the executive control network and between the executive control network and salience network was found to protect against relapse 30 days post-treatment. Effects may reflect a greater capacity to engage executive control processes when faced with opportunities to use cocaine.

    45. Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task

      Liam J Nestor, Anna Murphy, John McGonigle, Csaba Orban, Laurence Reed, Eleanor Taylor, Remy Flechais, Louise M Paterson, Dana Smith, Edward T Bullmore, Karen D Ersche, John Suckling, Roger Tait, Rebecca Elliott, Bill Deakin, Ilan Rabiner, Anne Lingford-Hughes, David J Nutt, Barbara Sahakian, Trevor W Robbins and ICCAM Consortium

      Version of Record online: 6 SEP 2016 | DOI: 10.1111/adb.12444

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      Opioid disturbances within dopamine fronto-striatal reward circuitry may confer an ongoing risk for relapse to drug rewards if there is a diminished incentive value of, and motivation to procure, non-drug rewards. Here, we show that acute naltrexone treatment does not remediate disturbances in fronto-striatal regions during non-drug reward anticipation in long-term abstinent alcoholic and polysubstance-dependent groups.

    46. Neural response to alcohol taste cues in youth: effects of the OPRM1 gene

      Ozlem Korucuoglu, Thomas E. Gladwin, Frank Baas, Roel J.T. Mocking, Henricus G. Ruhé, Paul F.C. Groot and Reinout W. Wiers

      Version of Record online: 5 SEP 2016 | DOI: 10.1111/adb.12440

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      In a young sample, we demonstrated reduced prefrontal activation and greater connectivity from the ventral-striatum to frontal regions, in the AG vs AA-variant of the OPRM1 gene (rs1799971) for alcohol > water-taste trials. These results indicate that adolescents carrying the G-allele may be more vulnerable for the alcohol to hijack the reward system in the absence of frontal control to regulate craving.

    47. D1, but not D2, receptor blockade within the infralimbic and medial orbitofrontal cortex impairs cocaine seeking in a region-specific manner

      Caitlin V. Cosme, Andrea L. Gutman, Wensday R. Worth and Ryan T. LaLumiere

      Version of Record online: 31 AUG 2016 | DOI: 10.1111/adb.12442

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      Infralimbic cortex (IL) and medial orbitofrontal cortex (mOFC) D1 receptors differentially mediate cocaine-seeking behavior. Intra-IL receptor blockade decreased cocaine seeking during cued reinstatement but had no effect on cocaine-primed reinstatement. In contrast, intra-mOFC D1 receptor blockade reduced cocaine seeking during all forms of reinstatement tested, whereas blocking D2 receptors in either region had no effect on cocaine seeking.

  5. Invited Reviews

    1. The gut in the brain: the effects of bariatric surgery on alcohol consumption

      Ashley N. Blackburn, Andras Hajnal and Lorenzo Leggio

      Version of Record online: 31 AUG 2016 | DOI: 10.1111/adb.12436

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      Recent rodent and human studies indicate that bariatric surgery, especially gastric bypass, may lead to the possible development of alcohol use disorder. Preliminary translational studies attribute changes in alcohol metabolism/pharmacokinetics resulting from bariatric surgery to be the most likely explanation. However, recent research reveals that alterations in brain reward processing may play an important role as well.

  6. Original Articles

    1. You have full text access to this OnlineOpen article
      Chronic exposure to cannabinoids during adolescence causes long-lasting behavioral deficits in adult mice

      J Tomas-Roig, E Benito, RC Agis-Balboa, F Piscitelli, S Hoyer-Fender, V Di Marzo and U Havemann-Reinecke

      Version of Record online: 31 AUG 2016 | DOI: 10.1111/adb.12446

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      Adolescent mice were subjected daily to WIN55212.2, then left undisturbed, and finally evaluated by behavioral testing at adulthood. Mice that received the drug during adolescence showed memory impairment, higher endocannabinoid levels and altered Rgs7 expression in adulthood, establishing a potential link to epigenetic changes.

    2. Behavioral and transcriptional patterns of protracted opioid self-administration in mice

      Urszula Skupio, Magdalena Sikora, Michal Korostynski, Agnieszka Wawrzczak-Bargiela, Marcin Piechota, Joanna Ficek and Ryszard Przewlocki

      Version of Record online: 31 AUG 2016 | DOI: 10.1111/adb.12449

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      The present study analyzes the phenotypic and molecular effects of protracted voluntary oral morphine or saccharin intake in mice. Animals self-administering morphine showed complex addiction-related behavioral pattern associated with long-lasting alterations in several groups of transcripts, including glucocorticoid receptor-dependent, circadian and insulin signaling pathway genes as revealed by the global gene expression in the striatum and prefrontal cortex.

    3. mGluR2/3 mediates short-term control of nicotine-seeking by acute systemic N-acetylcysteine

      Federico Moro, Alessandro Orrù, Claudio Marcello Marzo, Angelo Di Clemente and Luigi Cervo

      Version of Record online: 24 AUG 2016 | DOI: 10.1111/adb.12443

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      The present study shows how acute systemic N-acetylcysteine (100 mg/kg, i.p.) reduces nicotine-seeking behavior after reintroduction of nicotine-associated stimuli, without influencing the response elicited by stimuli conditioned to saccharin. Blocking the group II metabotropic glutamate receptors (mGluR2/3) with the selective antagonist LY341495 (1 mg/kg, i.p.) completely prevented the effect of N-acetylcysteine on nicotine-seeking behavior.

    4. Differential role of hypothalamic orexin/hypocretin neurons in reward seeking motivated by cocaine versus palatable food

      Rémi Martin-Fardon, Gabrielle Cauvi, Tony M. Kerr and Friedbert Weiss

      Version of Record online: 24 AUG 2016 | DOI: 10.1111/adb.12441

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      Hypothalamic orexin/hypocretin (Orx/Hcrt) neurons are thought to mediate both food-reinforced behaviors and behavior motivated by drugs of abuse. However, the relative role of the Orx/Hcrt system in behavior motivated by food versus drugs of abuse remains unclear. Here, we showed a role for the Orx/Hcrt system in perseverating, compulsive-like cocaine seeking but not behavior motivated by palatable food.

    5. Nicotine self-administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats

      Dolores B. Vazquez-Sanroman, Reyna D. Monje and Michael T. Bardo

      Version of Record online: 22 AUG 2016 | DOI: 10.1111/adb.12437

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      Nicotine self-administration remodeled perineuronal nets surrounding GABA interneurons in the ventral tegmental area and the orbitofrontal cortex, suggesting a new possible molecular target where nicotine-induced neuroplasticity takes place. Perineuronal net manipulations may prevent or reverse the different stages of tobacco addiction.

    6. Morphine treatment enhances glutamatergic input onto neurons of the nucleus accumbens via both disinhibitory and stimulating effect

      Kejing Yuan, Huan Sheng, Jiaojiao Song, Li Yang, Dongyang Cui, Qianqian Ma, Wen Zhang, Bin Lai, Ming Chen and Ping Zheng

      Version of Record online: 22 AUG 2016 | DOI: 10.1111/adb.12438

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      The NAc is an important site where morphine treatment produces its reinforcing effect on reward. We found that morphine treatment removes the inhibitory effect of DA on glutamatergic input onto NAc and potentiates glutamatergic input from BLA to NAc. Blockade of glutamatergic transmission in NAc or ablation of projection from BLA to NAc decreases morphine treatment-induced increase in locomotor activity.

    7. The infralimbic and prelimbic cortices contribute to the inhibitory control of cocaine-seeking behavior during a discriminative stimulus task in rats

      Andrea L. Gutman, Victoria A. Ewald, Caitlin V. Cosme, Wensday R. Worth and Ryan T. LaLumiere

      Version of Record online: 22 AUG 2016 | DOI: 10.1111/adb.12434

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      In a discriminative stimulus (DS) cocaine self-administration task, inactivation of the infralimbic or prelimbic cortex decreased performance accuracy and disinhibited behavioral responding. Inactivation of either structure decreased total infusions during both a DS task and an FR1 task. Combined with additional pharmacological manipulations, these results suggest that both regions contribute to the inhibitory control of drug-seeking behavior during a DS task.

    8. Dissociative role for dorsal hippocampus in mediating heroin self-administration and relapse through CDK5 and RhoB signaling revealed by proteomic analysis

      Zhong-Guo Chen, Xing Liu, Weisheng Wang, Fan Geng, Jing Gao, Chen-Ling Gan, Jing-Rui Chai, Ling He, Gang Hu, Hu Zhou and Jing-Gen Liu

      Version of Record online: 22 AUG 2016 | DOI: 10.1111/adb.12435

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      Cyclin-dependent kinase 5 (CDK5) and ras homolog family member B (RhoB) were up-regulated in the dorsal hippocampus (DH) of rats with a history of extended access to heroin. CDK5 signaling acts as a homeostatic compensatory mechanism to limit heroin-taking behavior, whereas RhoB signaling is required for the retrieval of addiction memory. The present study suggests that the DH can exert dissociative effects on heroin addiction through CDK5 and RhoB signaling.

    9. A dose–response estimate for acute alcohol use and risk of suicide attempt

      Guilherme Borges, Cheryl J. Cherpitel, Ricardo Orozco, Yu Ye, Maristela Monteiro, Wei Hao and Vikram Benegal

      Version of Record online: 10 AUG 2016 | DOI: 10.1111/adb.12439

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      Using data from a large and representative sample of patients from several countries and regions of the world, we found that every drink increased the risk of a suicide attempt by 30 percent, and 35 percent of all attempts were attributable to acute alcohol; even one to two drinks were associated with a sizable increase in the risk, and a dose–response was found for the relation between acute drinking and the risk of a suicide attempt up to 20 drinks.

    10. OPRM1 genotype interacts with serotonin system dysfunction to predict alcohol-heightened aggression in primates

      Carlos A Driscoll, Stephen G. Lindell, Melanie L Schwandt, Stephen J Suomi, J Dee Higley, Markus Heilig and Christina S Barr

      Version of Record online: 3 AUG 2016 | DOI: 10.1111/adb.12428

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      The rhesus macaque has been repeatedly shown to be useful for modeling genetic effects and G × E interactions that translate to the human condition. Results from the present study suggest the following: (1) that individuals who carry a variant in the OPRM1 gene experience more alcohol-induced stimulation are more likely react aggressively to provocation while intoxicated; (2) that subjects that exhibit a trait-like aggression marker (low CSF 5-HIAA) may be particularly prone to aggression during periods of intoxication if they are also carriers of the OPRM1 variant allele. By extension, these data suggest that the same factors that give rise to early, uncontrolled alcohol intake (impaired impulse control and increased alcohol-mediated reward) may also be risk factors for alcohol-induced aggressive responding. As OPRM1 genotype predicts clinical outcome following naltrexone treatment in alcohol dependent populations, these results may further suggest that naltrexone treatment may have promise for preventing or reducing alcohol-associated violence in selected patient populations.

    11. Intravenous self-administration of alcohol in rats—problems with translation to humans

      Anh D. Lê and Harold Kalant

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/adb.12429

      Intravenous self-administration (IVSA) of alcohol has been investigated across species. This systematic review shows that the amount of alcohol self-administered by rats is about 20–25 mg/kg/h, about 50- to 100-fold lower than by NHP or mice. Evidence to support such IVSA as well as potential mechanisms underlying such self-administration is discussed. The minute amounts of alcohol shown to maintain IVSA in rats challenge the relationship between their blood alcohol levels and the reinforcing effects of alcohol.

    12. Hypocretin/orexin knock-out mice display disrupted behavioral and dopamine responses to cocaine

      Jessica K. Shaw, Mark J. Ferris, Jason L. Locke, Zachary D. Brodnik, Sara R. Jones and Rodrigo A. España

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/adb.12432

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      The hypocretin/orexin system has been posited to influence reward and reinforcement processes through actions on the mesolimbic dopamine system. Using conditioned place preference, microdialysis, and fast-scan cyclic voltammetry, we demonstrate that hypocretin knockout mice fail to develop conditioned place preference for cocaine and display reduced dopamine release under baseline conditions and in response to cocaine.

    13. Reward and relief dimensions of temptation to drink: construct validity and role in predicting differential benefit from acamprosate and naltrexone

      Corey R. Roos, Karl Mann and Katie Witkiewitz

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/adb.12427

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      Study findings suggest that 10 items from the Temptation Scale of the Alcohol Abstinence Self-Efficacy Scale can be used to identify alcohol use disorder subtypes characterized by distinct pre-treatment patterns of reward and relief temptation to drink tendencies. Moreover, results indicated that acamprosate was particularly effective among a subgroup of clients with higher relief temptation than reward temptation.

    14. Prolonged withdrawal from cocaine self-administration affects prefrontal cortex- and basolateral amygdala–nucleus accumbens core circuits but not accumbens GABAergic local interneurons

      Anthony Purgianto, Michael E. Weinfeld and Marina E. Wolf

      Version of Record online: 25 JUL 2016 | DOI: 10.1111/adb.12430

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      We examined aspects of GABA transmission in nucleus accumbens (NAc) core after incubation of cocaine craving. Activity-dependent interneuron markers (e.g. parvalbumin) were unchanged, but local field potential recordings revealed differential adaptations in prefrontal cortex-NAc core and basolateral amygdala-NAc core circuits, some potentially involving GABA. Combined with other findings, our results suggest more pronounced changes in glutamate than GABA during incubation.

    15. You have full text access to this OnlineOpen article
      Caffeine-mediated BDNF release regulates long-term synaptic plasticity through activation of IRS2 signaling

      Cristina Lao-Peregrín, Jesús Javier Ballesteros, Miriam Fernández, Alfonsa Zamora-Moratalla, Ana Saavedra, María Gómez Lázaro, Esther Pérez-Navarro, Deborah Burks and Eduardo D. Martín

      Version of Record online: 25 JUL 2016 | DOI: 10.1111/adb.12433

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      Caffeine, a stimulant that enhances cognitive function, is the most widely consumed behaviorally active substance in the world. Here, we show that caffeine, at moderate doses of human consumption, induces an NMDA receptor-independent form of long-term potentiation and increases calcium-dependent brain-derived neurotrophic factor secretion, which is necessary for long-term potentiation maintenance through a TrkB-mediated process and activation of IRS2/PI3K/Akt signaling.

    16. Nucleus incertus corticotrophin-releasing factor 1 receptor signalling regulates alcohol seeking in rats

      Leigh C. Walker, Hanna E. Kastman, Jan A. Koeleman, Craig M. Smith, Christina J. Perry, Elena V. Krstew, Andrew L. Gundlach and Andrew J. Lawrence

      Version of Record online: 20 JUL 2016 | DOI: 10.1111/adb.12426

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      Bilateral injections into the rat nucleus incertus (NI) of CP376395 (500 ng/0.25 µl) attenuated yohimbine-induced reinstatement of alcohol seeking, whereas astressin-2B (200 ng/0.25 µl) had no significant effect. CRF-receptor 1, but not CRF-receptor 2, mRNA was upregulated in the NI following chronic ethanol intake. Corticotrophin-releasing factor (CRF) mRNA is expressed within the rat NI; CRF-containing neurons were confirmed by immunohistochemistry. NI neurons apparently contribute to alcohol seeking, via CRF-receptor 1 signaling. Chronic ethanol intake causes neuroadaptive changes in NI CRF and relaxin-3 systems.

    17. Varenicline, the clinically effective smoking cessation agent, restores probabilistic response reversal performance during withdrawal from nicotine

      Anne Jackson, Sarah Silk, Yazead Buhidma and Mohammed Shoaib

      Version of Record online: 20 JUL 2016 | DOI: 10.1111/adb.12423

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      Research in smokers has suggested that good performance monitoring is associated with successful abstinence from smoking. In a rodent model, execution of a probabilistic response reversal task was disrupted by nicotine withdrawal. Performance was restored by varenicline, suggesting the model to be useful for investigating new treatments to aid smoking cessation.

    18. The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens

      Eun Young Jang, Chae Ha Yang, David M. Hedges, Soo Phil Kim, Jun Yeon Lee, Tyler G. Ekins, Brandon T. Garcia, Hee Young Kim, Ashley C. Nelson, Nam Jun Kim and Scott C. Steffensen

      Version of Record online: 14 JUL 2016 | DOI: 10.1111/adb.12419

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      In this study, we utilized physiological, neurochemical, molecular, immunohistochemical and behavioral methodologies to show that methamphetamine (METH) enhances the production of reactive oxygen species, which leads to enhanced dopamine release in the nucleus accumbens and METH self-administration behavior. Drugs that reduce reactive oxygen species effectively reduced METH enhancement of dopamine release and subsequent self-administration behavior.

    19. You have full text access to this OnlineOpen article
      Effects of naltrexone on alcohol self-administration and craving: meta-analysis of human laboratory studies

      Christian S. Hendershot, Jeffrey D. Wardell, Andriy V. Samokhvalov and Jürgen Rehm

      Version of Record online: 14 JUL 2016 | DOI: 10.1111/adb.12425

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      This meta-analysis examined the aggregate effects of naltrexone versus placebo on alcohol self-administration and craving across human laboratory studies. Meta-analyses of self-administration (N = 490) and craving (N = 748) confirmed that naltrexone reduces laboratory consumption and acute craving relative to placebo. These results provide further evidence as to potential treatment mechanisms, also establishing effect sizes to inform future human laboratory trials.

    20. Neural correlates of impaired self-awareness of apathy, disinhibition and dysexecutive deficits in cocaine-dependent individuals

      Laura Moreno-López, Natalia Albein-Urios, José M. Martínez-González, Carles Soriano-Mas and Antonio Verdejo-García

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/adb.12422

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      In cocaine-dependent individuals, impaired self-awareness about apathy, disinhibition and dysexecutive symptoms is underpinned by structural brain phenotypes involving the dorsal striatum, the orbitofrontal cortex and the dorsolateral prefrontal cortex.

    21. Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2/D3 dopamine system

      Philippe Pfeifer, Oliver Tüscher, Hans Georg Buchholz, Gerhard Gründer, Ingo Vernaleken, Michael Paulzen, Ulrich S. Zimmermann, Stephan Maus, Klaus Lieb, Thomas Eggermann, Christoph Fehr and Mathias Schreckenberger

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/adb.12424

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      We applied PET imaging using the dopamine D2/D3 ligand [18F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol. In the alcohol condition, no response (reduction of BPND) was observed in striatal and extrastriatal regions. We found a positive correlation for “liking” alcohol in extrastriatal regions.

    22. Harm reduction—a systematic review on effects of alcohol reduction on physical and mental symptoms

      Katrin Charlet and Andreas Heinz

      Version of Record online: 29 JUN 2016 | DOI: 10.1111/adb.12414

      This systematic review shows that a reduction of the individual alcohol consumption can contribute to a minimization of various physical and mental health risks in harmful, hazardous or alcohol-dependent drinkers (together with socioeconomic cost benefits) within a harm reduction approach. Here, individuals with heightened vulnerability further benefit significantly from alcohol reduction (e.g. individuals with hypertension, hepatitis C, psychiatric co-morbidities, pregnant or breastfeeding women, and also among adolescents and young adults).


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