Addiction Biology

Cover image for Vol. 19 Issue 2

March 2014

Volume 19, Issue 2

Pages i–ii, 145–315

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. PRECLINICAL STUDIES
    4. HUMAN IMAGING STUDIES
    5. HUMAN NEUROIMAGING STUDY
    6. HUMAN STUDY
    7. HUMAN EPIGENETIC STUDY
    8. HUMAN GENETIC STUDY
    1. Issue Information (pages i–ii)

      Article first published online: 20 FEB 2014 | DOI: 10.1111/adb.12091

  2. PRECLINICAL STUDIES

    1. Top of page
    2. Issue Information
    3. PRECLINICAL STUDIES
    4. HUMAN IMAGING STUDIES
    5. HUMAN NEUROIMAGING STUDY
    6. HUMAN STUDY
    7. HUMAN EPIGENETIC STUDY
    8. HUMAN GENETIC STUDY
    1. Methylphenidate and cocaine self-administration produce distinct dopamine terminal alterations (pages 145–155)

      Erin S. Calipari, Mark J. Ferris, James R. Melchior, Kristel Bermejo, Ali Salahpour, David C. S. Roberts and Sara R. Jones

      Article first published online: 28 MAR 2012 | DOI: 10.1111/j.1369-1600.2012.00456.x

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      While methylphenidate and cocaine have similar inhibitory mechanisms of action at the dopamine transporter (DAT), the neurochemical consequences of i.v.self-administration of the two drugs are completely different. While a five-day history of cocaine self-administration selectively reduced cocaine potency at the DAT without affecting methylphenidate potency, methylphenidate self-administration selectively increased its own potency, as measured using voltammetry in the nucleus accumbens core. These findings suggest that the factors governing dopamine system adaptations are more complicated than simple DAT blockade.

    2. Sex differences in yohimbine-induced increases in the reinforcing efficacy of nicotine in adolescent rats (pages 156–164)

      Sophia Li, Sheng Zou, Kathleen Coen, Douglas Funk, Megan J. Shram and A.D. Lê

      Article first published online: 11 JUL 2012 | DOI: 10.1111/j.1369-1600.2012.00473.x

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      Stress is an important factor in adolescent smoking. Females more readily develop addiction to smoking, have more difficulty quitting, and show enhanced stress responses. We therefore investigated how stress affects the reinforcing efficacy of nicotine in male and female rats trained to self-administer nicotine intravenously as adolescents. Compared to males, females had greater increases in progressive ratio breakpoints, that also occurred at lower nicotine infusion doses, in response to the pharmacological stressor yohimbine, suggesting that the adolescent females were more sensitive to stress-induced potentiation of nicotine’s reinforcing efficacy.

    3. Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) (pages 165–174)

      Lucas R. Watterson, Peter R. Kufahl, Natali E. Nemirovsky, Kaveish Sewalia, Megan Grabenauer, Brian F. Thomas, Julie A. Marusich, Scott Wegner and M. Foster Olive

      Article first published online: 11 JUL 2012 | DOI: 10.1111/j.1369-1600.2012.00474.x

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      The use and abuse of designer stimulant such as 3,4-methylenedioxypyrovalerone (MDPV), often sold as “bath salts”, has increased dramatically in recent years.

      The present study reveals that MDPV supports robust intravenous self-administration behavior across a range of doses, leads to escalation of intake with prolonged access, and produces decreases in brain stimulation reward thresholds. Together, these results reveal potent rewarding and reinforcing effects of MDPV, suggestive of a high degree of addiction potential in humans.

    4. Reduced ethanol consumption and preference in cocaine- and amphetamine-regulated transcript (CART) knockout mice (pages 175–184)

      Armando G. Salinas, Chinh T. Q. Nguyen, Dara Ahmadi-Tehrani and Richard A. Morrisett

      Article first published online: 24 JUL 2012 | DOI: 10.1111/j.1369-1600.2012.00475.x

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      We utilized a Cocaine- and amphetamine-regulated transcript knockout (KO) mouse model to investigate the role of CART in ethanol-appetitive behaviors. An unlimited-access paradigm was used to compare ethanol appetitive behaviors between CART wild type (WT) and KO mice. CART KO mice consumed and preferred ethanol less than their WT counterparts in both sexes. Taken together, these data demonstrate a role for CART in ethanol appetitive behaviors and as a possible therapeutic drug target for alcoholism and abstinence enhancement.

    5. Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys (pages 185–194)

      Lin Sun, Qi Li, Qing Li, Yuzhe Zhang, Dexiang Liu, Hong Jiang, Fang Pan and David T. Yew

      Article first published online: 12 NOV 2012 | DOI: 10.1111/adb.12004

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      Ketamine becomes an increasingly popular drug in the worldwide. The current study detected apoptotic markers, including Bax, Bcl-2 and caspase-3 in the prefrontal cortex of adolescent male cynomolgus monkeys after 1 or 6 months of subanesthetic ketamine administration (1 mg/kg, i.v.). The results of Bax and caspase-3 in the 6-month ketamine-treated group showed significant increases compared with the control group, despite a decrease in Bcl-2, which was not significant. There were no significant differences in the 1-month ketamine-treated group. So ketamine might produce deficits in brain functions, involving the activation of apoptotic pathways in the prefrontal cortex.

    6. A novel mGluR5 antagonist, MFZ 10-7, inhibits cocaine-taking and cocaine-seeking behavior in rats (pages 195–209)

      Thomas M. Keck, Mu-Fa Zou, Guo-Hua Bi, Hai-Ying Zhang, Xiao-Fei Wang, Hong-Ju Yang, Ratika Srivastava, Eliot L. Gardner, Zheng-Xiong Xi and Amy Hauck Newman

      Article first published online: 3 SEP 2013 | DOI: 10.1111/adb.12086

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      The mGluR5 negative allosteric modulators (NAMs) MPEP and MTEP are highly promising in treatment of addiction in experimental animals. However, their translational potential for use in humans is very low because of their off-target effects and short half-lives. Here, we report that MFZ 10-7, a novel mGluR5 NAM, is more potent and selective than MPEP or MTEP in both in vitro binding and functional assays, and similarly effective as MTEP in attenuation of cocaine-taking and cocaine-seeking behavior in rats.

    7. Deciphering the relationship between vulnerability to ethanol-induced behavioral sensitization and ethanol consumption in outbred mice (pages 210–224)

      Rémi Legastelois, Béatrice Botia, Fabien Coune, Jérôme Jeanblanc and Mickaël Naassila

      Article first published online: 28 OCT 2013 | DOI: 10.1111/adb.12104

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      Ethanol-induced behavioral sensitization (EIBS) may play a role in alcohol dependence, but its impact on alcohol abuse is not clear. Here we showed that outbred Swiss mice susceptibility to EIBS is inversely correlated with voluntary ethanol consumption. EIBS development increased subsequent ethanol intake and the less mice are sensitized the more they increase their ethanol intake; however, resistant mice were sensitive to ethanol adulteration with quinine, whereas sensitized ones maintained their ethanol intake levels, therefore exhibiting a compulsive-like drinking pattern.

    8. Cluster and meta-analyses on factors influencing stress-induced alcohol drinking and relapse in rodents (pages 225–232)

      Hamid R. Noori, Sandra Helinski and Rainer Spanagel

      Article first published online: 20 FEB 2014 | DOI: 10.1111/adb.12125

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      Although there is a good qualitative description of the determinants of alcohol consumption in rodents, the magnitude of the variables influencing stress-induced ethanol intake and relapse and its dynamics are poorly understood. We therefore conducted a clustered meta-analysis on stress-induced alcohol consumption in 1520 rats. Two-step clustering of the literature-derived dataset suggests that stress-induced increase of alcohol consumption is best observed in adult male Wistar rats exposed to either foot shocks or forced swim stress within a free-choice drinking paradigm.

    9. N-(2-methyl-6-benzoxazolyl)-N′-1,5-naphthyridin-4-yl urea (SB334867), a hypocretin receptor-1 antagonist, preferentially prevents ethanol seeking: comparison with natural reward seeking (pages 233–236)

      Rémi Martin-Fardon and Friedbert Weiss

      Article first published online: 26 JUL 2012 | DOI: 10.1111/j.1369-1600.2012.00480.x

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      Orexins/hypocretins (Orx/Hcrt) are hypothalamic peptides that regulate a wide range of physiological processes that are recruited by drugs of abuse. We tested the effect of the specific Orx/Hcrt receptor-1 (Hcrt-r1) antagonist SB334867 on reinstatement elicited by ethanol-associated stimuli vs. stimuli associated with a conventional reinforcer (SuperSac, consisting of 3% glucose and 0.125% saccharin w/v). SB334867 dose-dependently reduced reinstatement induced by the ethanol- but not SuperSac-associated stimuli, supporting a differential role for Hcrt-r1 in mediating ethanol seeking vs. natural reward seeking.

    10. Anti-addiction drug ibogaine inhibits hERG channels: a cardiac arrhythmia risk (pages 237–239)

      Xaver Koenig, Michael Kovar, Stefan Boehm, Walter Sandtner and Karlheinz Hilber

      Article first published online: 28 MAR 2012 | DOI: 10.1111/j.1369-1600.2012.00447.x

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      Ibogaine, an alkaloid derived from the African shrub Tabernanthe iboga, has shown promising anti-addictive properties in humans. Although not licensed as therapeutic drug, and despite evidence that ibogaine may disturb the rhythm of the heart, this alkaloid is currently used as an anti-addiction drug in alternative medicine. Here, we report that therapeutic concentrations of ibogaine reduce currents through human ether-a-go-go-related gene potassium channels. Thereby, we provide a mechanism by which ibogaine may generate life-threatening cardiac arrhythmias.

  3. HUMAN IMAGING STUDIES

    1. Top of page
    2. Issue Information
    3. PRECLINICAL STUDIES
    4. HUMAN IMAGING STUDIES
    5. HUMAN NEUROIMAGING STUDY
    6. HUMAN STUDY
    7. HUMAN EPIGENETIC STUDY
    8. HUMAN GENETIC STUDY
    1. Brain activation to cocaine cues and motivation/treatment status (pages 240–249)

      James J. Prisciandaro, Aimee L. McRae-Clark, Hugh Myrick, Scott Henderson and Kathleen T. Brady

      Article first published online: 28 MAR 2012 | DOI: 10.1111/j.1369-1600.2012.00446.x

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      The present study investigated the relationship between motivation to change cocaine use and cue-elicited brain activity in cocaine-dependent individuals using two conceptualizations of “motivation to change:” current treatment status and self-reported motivation to change. Thirty-eight cocaine dependent individuals completed an assessment and an fMRI cocaine cue-reactivity task. Both treatment-seeking (n=14) and motivated participants had lower activation to cocaine cues in a wide variety of regions in the frontal, occipital, temporal, and cingulate cortices relative to non-treatment-seeking and less motivated participants.

    2. Differences in regional cerebral blood flow response to a 5HT3 antagonist in early- and late-onset cocaine-dependent subjects (pages 250–261)

      Bryon Adinoff, Michael D. Devous, Mark J. Williams, Thomas S. Harris, Susan E. Best, Hongyun Dong and Tanya Zielinski

      Article first published online: 28 MAR 2012 | DOI: 10.1111/j.1369-1600.2012.00450.x

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      5-hydroxytryptamine 3 (5HT3) receptors modulate mesostriatal dopaminergic transmission and the 5HT3 antagonist ondansetron is effective in treating early-onset, but not late-onset, alcohol-dependent subjects. In this study, regional cerebral blood flow (rCBF) was assessed following the intravenous administration of ondansetron to early- (n=10) and late-onset (n=10) cocaine-dependent and 22 control participants. Group differences in rCBF were observed in the rostral anterior cingulate, posterior parahippocampus, anterior insula, and subthalamic nucleus. Age of cocaine use onset appears to be associated with serotonergic biosignatures.

    3. Extended-release naltrexone modulates brain response to drug cues in abstinent heroin-dependent patients (pages 262–271)

      Daniel D. Langleben, Kosha Ruparel, Igor Elman, James W. Loughead, Elliot L. Busch, James Cornish, Kevin G. Lynch, Elie S. Nuwayser, Anna R. Childress and Charles P. O'Brien

      Article first published online: 2 JUL 2012 | DOI: 10.1111/j.1369-1600.2012.00462.x

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      We studied the effect of extended-release naltrexone (XRNTX) on the brain fMRI response to heroin-related cues in 17 detoxified heroin users. On XRNTX there was a decrease in the limbic and increase in the prefrontal response to drug cues. Higher plasma levels of naltrexone�s metabolite, 6-β-naltrexol, were associated with larger reduction in the fMRI response to drug cues in the precentral, caudate and amygdala regions. Brain response to drug cues and 6-β-naltrexol levels warrant further study as potential therapeutic biomarkers of XRNTX.

    4. Functional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects (pages 272–281)

      Antonio Verdejo-Garcia, Oren Contreras-Rodríguez, Francina Fonseca, Aida Cuenca, Carles Soriano-Mas, Joan Rodriguez, Ricardo Pardo-Lozano, Laura Blanco-Hinojo, Susana de Sola Llopis, Magí Farré, Marta Torrens, Jesús Pujol and Rafael de la Torre

      Article first published online: 11 JUL 2012 | DOI: 10.1111/j.1369-1600.2012.00472.x

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      During the functional resonance imaging moral decision-making task (e.g., “would you throw a dying person into the sea to float a lifeboat full of survivors?”), cocaine dependent users displayed significantly reduced signal in brain regions involved in generating and instantiating emotions (i.e., insula, anterior cingulate cortex and brainstem periacqueductal gray). We reason that cocaine dependent users exhibit blunted responsiveness of the brain network that normally anticipates potentially aversive emotional consequences of complex social decisions.

  4. HUMAN NEUROIMAGING STUDY

    1. Top of page
    2. Issue Information
    3. PRECLINICAL STUDIES
    4. HUMAN IMAGING STUDIES
    5. HUMAN NEUROIMAGING STUDY
    6. HUMAN STUDY
    7. HUMAN EPIGENETIC STUDY
    8. HUMAN GENETIC STUDY
    1. Relationship between working-memory network function and substance use: a 3-year longitudinal fMRI study in heavy cannabis users and controls (pages 282–293)

      Janna Cousijn, Wilhelmina A. M. Vingerhoets, Laura Koenders, Lieuwe de Haan, Wim van den Brink, Reinout W. Wiers and Anna E. Goudriaan

      Article first published online: 25 NOV 2013 | DOI: 10.1111/adb.12111

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      The aim of this three-year longitudinal neuroimaging study was to investigate the relationship between substance use and working-memory network function over time in heavy cannabis users and controls. These results suggest that sustained moderate to heavy levels of cannabis, nicotine, alcohol, and illegal psychotropic substance use do not change working-memory network functionality. Moreover, baseline network-functionality did not predict cannabis use and related problems three years later, warranting longitudinal studies in more chronic or dependent cannabis users.

  5. HUMAN STUDY

    1. Top of page
    2. Issue Information
    3. PRECLINICAL STUDIES
    4. HUMAN IMAGING STUDIES
    5. HUMAN NEUROIMAGING STUDY
    6. HUMAN STUDY
    7. HUMAN EPIGENETIC STUDY
    8. HUMAN GENETIC STUDY
    1. Neural correlates of attentional bias for smoking cues: modulation by variance in the dopamine transporter gene (pages 294–304)

      Reagan R. Wetherill, Kanchana Jagannathan, Falk W. Lohoff, Ronald Ehrman, Charles P. O'Brien, Anna Rose Childress and Teresa R. Franklin

      Article first published online: 12 OCT 2012 | DOI: 10.1111/j.1369-1600.2012.00507.x

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      The dopamine transporter (DAT) SLC6A3 genotype exerts profound effects on limbic responses to smoking cues (SCs). One potential mechanism underlying these effects is greater attentional bias for SCs. Here, we explored associations between attentional bias and neural responses to SCs using perfusion fMRI and a visual dot-probe attentional bias task among smokers genotyped for the SLC6A3 polymorphism. Findings suggest that genetic variation in the DAT gene influences brain responses associated with attentional bias, providing additional support for a SC-vulnerable endophenotype.

  6. HUMAN EPIGENETIC STUDY

    1. Top of page
    2. Issue Information
    3. PRECLINICAL STUDIES
    4. HUMAN IMAGING STUDIES
    5. HUMAN NEUROIMAGING STUDY
    6. HUMAN STUDY
    7. HUMAN EPIGENETIC STUDY
    8. HUMAN GENETIC STUDY
    1. Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age (pages 305–311)

      Vanessa Nieratschker, Martin Grosshans, Josef Frank, Jana Strohmaier, Christoph von der Goltz, Osman El-Maarri, Stephanie H. Witt, Sven Cichon, Markus M. Nöthen, Falk Kiefer and Marcella Rietschel

      Article first published online: 16 APR 2012 | DOI: 10.1111/j.1369-1600.2012.00459.x

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      Chronic alcohol dependence is associated with dysfunctional dopaminergic neurotransmission. A possible reason may be altered methylation of the dopamine transporter gene (DAT). Our study detected no differences in DAT methylation between alcohol dependent patients and population-based controls. However, patients with more severe craving showed a trend towards lower DAT methylation. Furthermore, DAT methylation levels increased with age, particularly in the patient group. This suggests that hypermethylation in alcohol dependent patients is a consequence, rather than a cause, of the disorder.

  7. HUMAN GENETIC STUDY

    1. Top of page
    2. Issue Information
    3. PRECLINICAL STUDIES
    4. HUMAN IMAGING STUDIES
    5. HUMAN NEUROIMAGING STUDY
    6. HUMAN STUDY
    7. HUMAN EPIGENETIC STUDY
    8. HUMAN GENETIC STUDY
    1. Association of GATA4 sequence variation with alcohol dependence (pages 312–315)

      Victor M. Karpyak, Stacey J. Winham, Joanna M. Biernacka, Julie M. Cunningham, Kriste A. Lewis, Jennifer R. Geske, Colin L. Colby, Osama A. Abulseoud, Daniel K. Hall-Flavin, Larissa L. Loukianova, Terry D. Schneekloth, Mark A. Frye, John A. Heit and David A. Mrazek

      Article first published online: 1 AUG 2012 | DOI: 10.1111/j.1369-1600.2012.00482.x

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      Association between alcohol dependence and GATA4 SNPs.

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