Addiction Biology

Cover image for Vol. 19 Issue 3

May 2014

Volume 19, Issue 3

Pages 317–515

  1. REVIEW

    1. Top of page
    2. REVIEW
    3. BRIEF REPORT: PRECLINICAL STUDIES
    4. PRECLINICAL STUDIES
    5. HUMAN NEUROIMAGING STUDIES
    6. HUMAN NEUROIMAGING STUDISE
    7. BRIEF REPORT: HUMAN STUDY
    8. HUMAN STUDIES
    9. HUMAN GENETIC STUDY
    1. The cerebellum and addiction: insights gained from neuroimaging research (pages 317–331)

      Eric A. Moulton, Igor Elman, Lino R. Becerra, Rita Z. Goldstein and David Borsook

      Article first published online: 15 OCT 2013 | DOI: 10.1111/adb.12101

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      Although cerebellar alterations have been consistently noted in the addiction literature, the pathophysiology of this link remains unclear. This review article considers the potential role of the cerebellum in addiction, the cerebellar structural alterations linked to addiction, the functional neuroimaging evidence linking the cerebellum with addiction, and proposes a model for addiction that underscores the role of the cerebellum.

  2. BRIEF REPORT: PRECLINICAL STUDIES

    1. Top of page
    2. REVIEW
    3. BRIEF REPORT: PRECLINICAL STUDIES
    4. PRECLINICAL STUDIES
    5. HUMAN NEUROIMAGING STUDIES
    6. HUMAN NEUROIMAGING STUDISE
    7. BRIEF REPORT: HUMAN STUDY
    8. HUMAN STUDIES
    9. HUMAN GENETIC STUDY
    1. Susceptibility to ethanol withdrawal seizures is produced by BK channel gene expression (pages 332–337)

      Alfredo Ghezzi, Harish R. Krishnan and Nigel S. Atkinson

      Article first published online: 27 JUN 2012 | DOI: 10.1111/j.1369-1600.2012.00465.x

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      Alcohol withdrawal seizures are part of the symptomatology of severe alcohol dependence and are believed to originate from neural adaptations that counter the depressant effects of alcohol. When alcohol is withheld these pro-excitatory adaptations are uncovered and can be sufficient to generate a seizure. Using the Drosophila model organism, we demonstrate a central role for the BK-type Ca2+-activated K+ channel gene slo in the production of alcohol withdrawal seizures.

    2. Role of ventral subiculum in context-induced reinstatement of heroin seeking in rats (pages 338–342)

      Jennifer M. Bossert and Anna L. Stern

      Article first published online: 12 DEC 2012 | DOI: 10.1111/adb.12015

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      In rats, re-exposure to heroin-paired contexts after extinction of lever-pressing in a different context reinstates heroin seeking. Previous reports indicate that ventral hippocampus plays a critical role in cocaine-, cue-, and context-induced reinstatement of cocaine seeking. Here, we found that reversible inactivation of ventral subiculum, the output region of ventral hippocampus, decreased context-induced reinstatement of heroin seeking. Our findings, together with previous studies on cocaine seeking, indicate a critical role of ventral subiculum in context-induced relapse across drug classes.

  3. PRECLINICAL STUDIES

    1. Top of page
    2. REVIEW
    3. BRIEF REPORT: PRECLINICAL STUDIES
    4. PRECLINICAL STUDIES
    5. HUMAN NEUROIMAGING STUDIES
    6. HUMAN NEUROIMAGING STUDISE
    7. BRIEF REPORT: HUMAN STUDY
    8. HUMAN STUDIES
    9. HUMAN GENETIC STUDY
    1. NrCAM-regulating neural systems and addiction-related behaviors (pages 343–353)

      Hiroki Ishiguro, Frank S. Hall, Yasue Horiuchi, Takeshi Sakurai, Akitoyo Hishimoto, Martin Grumet, George R. Uhl, Emmanuel S. Onaivi and Tadao Arinami

      Article first published online: 11 JUL 2012 | DOI: 10.1111/j.1369-1600.2012.00469.x

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      NrCAM has a role in substance abuse, possibly through its effects on behavioral traits that may affect addiction vulnerability, including novelty seeking, obsessive compulsion and responses to aversive or anxiety-provoking stimuli. Glutaminase appears to be involved in NrCAM-related molecular pathway, and a treatment with inhibitor of the enzyme PLG altered some mice's phenotypes in alcohol preference and in anxiety-like behavior. Thus, NrCAM could affect addiction-related behaviors via at least partially modulation of some glutamatargic pathways and neural function in brain.

    2. Brain region- and sex-specific alterations in DAMGO-stimulated [35S]GTPγS binding in mice with Oprm1 A112G (pages 354–361)

      Yu-Jun Wang, Peng Huang, Julie A. Blendy and Lee-Yuan Liu-Chen

      Article first published online: 2 AUG 2012 | DOI: 10.1111/j.1369-1600.2012.00484.x

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      We examined whether A118G SNP of the human µ opioid receptor gene affected G protein activation in a mouse model with the equivalent substitution. DAMGO-stimulated [35S]GTPgS binding in brain regions was examined by autoradiography. G/G mice (males and females) exhibited lower [35S]GTPgS binding in VTA than A/A. In NAc core, female G/G mice displayed lower [35S]GTPgS binding than female A/A. In G/G mice, males showed higher [35S]GTPgS binding than females in cingulate cortex, CPu, NAc core, thalamus and amygdala.

    3. Inhibitory effects of SA4503 on the rewarding effects of abused drugs (pages 362–369)

      Tomohisa Mori, Mahardian Rahmadi, Kazumi Yoshizawa, Toshimasa Itoh, Masahiro Shibasaki and Tsutomu Suzuki

      Article first published online: 31 AUG 2012 | DOI: 10.1111/j.1369-1600.2012.00488.x

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      Previous findings have shown that sigma-1 receptors are upregulated by the self-administration of methamphetamine, whereas sigma-1 receptor antisense can attenuate the behavioral effects of psychostimulants in rodents. We examined the effects of the selective sigma-1 receptor agonist SA4503 on the rewarding effects of abused drugs. SA4503 significantly attenuated the abused drug-induced place preference. These results suggest that SA4503 inhibits the rewarding effects of abused drugs.

    4. Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine (pages 370–379)

      Emily C. Eastwood and Tamara J. Phillips

      Article first published online: 12 NOV 2012 | DOI: 10.1111/adb.12003

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      Lines of mice selectively bred for either high or low free-choice methamphetamine intake were tested for responses to the non-selective opioid receptor agonist, morphine and the mu-opioid receptor specific agonist, fentanyl. The selected mouse lines did not differ in analgesic response, but low methamphetamine intake was associated with higher sensitivity to the locomotor activating effects of both opioids. These data indicate shared genetic influence on methamphetamine intake and opioid-induced activation. Opioid receptor regulated systems may be involved in methamphetamine intake.

    5. NMDA receptors in the midbrain play a critical role in dopamine-mediated hippocampal synaptic potentiation caused by morphine (pages 380–391)

      Ling Hu, Xiang-Hong Jing, Cai-Lian Cui, Guo-Gang Xing and Bing Zhu

      Article first published online: 19 NOV 2012 | DOI: 10.1111/adb.12010

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      A single exposure to drugs of abuse produces an NMDAR-dependent synaptic potentiation at excitatory synapses of VTA dopamine neurons. Hippocampal DA release modulates hippocampal plasticity and drug-associated memories. We find that intra-VTA but not intra-hippocampus injection of morphine evoked hippocampal synaptic potentiation. Local hippocampal dopamine D1 receptors are required in the morphine-induced synaptic potentiation and CPP. Moreover, both NMDAR activation in the VTA and VTA/hippocampus dopaminergic connections are essential for the morphine-evoked potentiation and CPP.

    6. Long-lasting, experience-dependent alcohol preference in Drosophila (pages 392–401)

      Raniero L. Peru y Colón de Portugal, Shamsideen A. Ojelade, Pranav S. Penninti, Rachel J. Dove, Matthew J. Nye, Summer F. Acevedo, Antonio Lopez, Aylin R. Rodan and Adrian Rothenfluh

      Article first published online: 28 OCT 2013 | DOI: 10.1111/adb.12105

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      The study of addiction in Drosophila benefits from assays with high face validity and throughput. Here, we establish a novel ethanol consumption preference assay, which allows for fast, and accurate preference measurements in individual flies. We show that naïve flies do not prefer to consume ethanol, but various pre-exposures, such as ethanol vapor or voluntary ethanol consumption, induce ethanol preference. This ethanol-primed preference is long lasting and is not driven by calories contained in ethanol during the consumption choice.

  4. HUMAN NEUROIMAGING STUDIES

    1. Top of page
    2. REVIEW
    3. BRIEF REPORT: PRECLINICAL STUDIES
    4. PRECLINICAL STUDIES
    5. HUMAN NEUROIMAGING STUDIES
    6. HUMAN NEUROIMAGING STUDISE
    7. BRIEF REPORT: HUMAN STUDY
    8. HUMAN STUDIES
    9. HUMAN GENETIC STUDY
    1. Increased neural activity during high working memory load predicts low relapse risk in alcohol dependence (pages 402–414)

      Katrin Charlet, Anne Beck, Anne Jorde, Lioba Wimmer, Sabine Vollstädt-Klein, Jürgen Gallinat, Henrik Walter, Falk Kiefer and Andreas Heinz

      Article first published online: 22 OCT 2013 | DOI: 10.1111/adb.12103

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      Imaging studies on working memory in alcohol-dependent patients (ADP) compared to controls (HC) indicate that inefficient information processing requires compensatory brain activation to perform normally. However, can neural activation patterns predict relapse behavior? We combined functional and structural brain analyses of 40 ADP and 40 HC and assessed prospective relapse risk. Our findings suggest that in prospective abstainers, higher functional engagement of behavioral control brain areas (BA10, 45, 47, 6, 8) may constitute a resilience factor associated with good treatment outcome.

    2. Re-appraisal of negative emotions in cocaine dependence: dysfunctional corticolimbic activation and connectivity (pages 415–426)

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

      Article first published online: 14 SEP 2012 | DOI: 10.1111/j.1369-1600.2012.00497.x

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      Using a cognitive reappraisal task during fMRI scanning we showed that cocaine dependent users display increased right dorsolateral prefrontal cortex (rDLPFC) activation while experiencing negative emotions, and decreased right inferior frontal gyrus (rIFG) activation while attempting to regulate these emotions. Connectivity analyses further showed that cocaine users exhibit increased connectivity between rDLPFC and regions involved in emotional appraisal during the experience of emotions, and decreased connectivity between the rIFG and the amygdala during the regulation of negative emotions.

    3. Neural network activation during a stop-signal task discriminates cocaine-dependent from non-drug-abusing men (pages 427–438)

      Amanda Elton, Jonathan Young, Sonet Smitherman, Robin E. Gross, Tanja Mletzko and Clinton D. Kilts

      Article first published online: 12 DEC 2012 | DOI: 10.1111/adb.12011

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      Cocaine dependence is defined by deficits in inhibitory behavioral control. We assessed whether patterns of neural processing related to inhibitory motor control reliably and accurately discriminate cocaine-dependent and control samples of men. An independent component analysis of fMRI time courses identified neural processing networks associated with five sub-processes of the stop-signal task. Linear discriminant analysis was used to train and independently test an accurate multivariate pattern classifier. Cocaine addiction classification scores predicted trait impulsiveness and level of lifetime cocaine use.

    4. Neural activation during processing of aversive faces predicts treatment outcome in alcoholism (pages 439–451)

      Katrin Charlet, Florian Schlagenhauf, Anne Richter, Karina Naundorf, Lina Dornhof, Christopher E. J. Weinfurtner, Friederike König, Bernadeta Walaszek, Florian Schubert, Christian A. Müller, Stefan Gutwinski, Annette Seissinger, Lioba Schmitz, Henrik Walter, Anne Beck, Jürgen Gallinat, Falk Kiefer and Andreas Heinz

      Article first published online: 7 MAR 2013 | DOI: 10.1111/adb.12045

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      While neuropsychological studies reported decoding deficits of emotional faces in alcohol-dependent patients, imaging studies revealed reduced prefrontal/limbic activation during emotional face processing. We investigated whether this reduced neuronal activation is mediated by brain atrophy and whether it interacts with treatment outcome. We combined structural and functional brain analyses (Hariri faces-task) on data sets of 33 detoxified alcoholics and 33 matched controls. Low atrophy and high activation of rostral ACC elicited by affective faces appear to be resilience factors predicting better treatment outcome.

    5. Impaired emotional empathy and related social network deficits in cocaine users (pages 452–466)

      Katrin H. Preller, Lea M. Hulka, Matthias Vonmoos, Daniela Jenni, Markus R. Baumgartner, Erich Seifritz, Isabel Dziobek and Boris B. Quednow

      Article first published online: 25 JUN 2013 | DOI: 10.1111/adb.12070

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      As social functioning plays a crucial role in the development of drug dependence, we investigated mental perspective-taking (‘theory-of-mind’) and emotional/cognitive empathy in 69 recreational and 31 dependent cocaine users. Cocaine users showed less emotional empathy and a smaller social network, whereas their cognitive empathy was not impaired. Additionally, dependent cocaine users were worse in mental perspective-taking. In conclusion, social cognition impairments in cocaine users were related to real-life social functioning and should therefore be considered in therapy and prevention strategies.

  5. HUMAN NEUROIMAGING STUDISE

    1. Top of page
    2. REVIEW
    3. BRIEF REPORT: PRECLINICAL STUDIES
    4. PRECLINICAL STUDIES
    5. HUMAN NEUROIMAGING STUDIES
    6. HUMAN NEUROIMAGING STUDISE
    7. BRIEF REPORT: HUMAN STUDY
    8. HUMAN STUDIES
    9. HUMAN GENETIC STUDY
    1. Functional imaging of an alcohol-Implicit Association Test (IAT) (pages 467–481)

      Susan L. Ames, Jerry L. Grenard, Qinghua He, Alan W. Stacy, Savio W. Wong, Lin Xiao, Gui Xue and Antoine Bechara

      Article first published online: 4 JUL 2013 | DOI: 10.1111/adb.12071

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      This research assessed activation in neural substrates involved in implicit associative processes through fMRI of an alcohol-Implicit Association Test (IAT) focused on positive outcomes of alcohol use. Imaging data revealed heavy drinkers showed greater activity during compatible trials relative to incompatible trials in the left putamen and insula while no significant difference between conditions was found in the light drinkers. This is the first study to evaluate the neural mechanisms elicited by an alcohol-IAT, increasing understanding of associative habit processes.

  6. BRIEF REPORT: HUMAN STUDY

    1. Top of page
    2. REVIEW
    3. BRIEF REPORT: PRECLINICAL STUDIES
    4. PRECLINICAL STUDIES
    5. HUMAN NEUROIMAGING STUDIES
    6. HUMAN NEUROIMAGING STUDISE
    7. BRIEF REPORT: HUMAN STUDY
    8. HUMAN STUDIES
    9. HUMAN GENETIC STUDY
    1. Serum brain-derived neurotrophic factor levels were reduced during methamphetamine early withdrawal (pages 482–485)

      Pao-Huan Chen, Ming-Chi Huang, Ying-Ching Lai, Po-Yu Chen and Hsing-Cheng Liu

      Article first published online: 28 MAR 2012 | DOI: 10.1111/j.1369-1600.2012.00444.x

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      In this study, we found that serum brain-derived neurotrophic factor (BDNF) levels were significantly and constantly lower in 59 human methamphetamine (METH) abusers during the first 3 weeks of withdrawal than those of the age- and sex-matched healthy controls. The greatest predictive validity for serum BDNF levels was provided by METH abuse itself but not other confounders in the multiple regression analysis. Findings suggest that METH abusers have a substantial BDNF down-regulation and possibly neuroprotective dysfunction after repetitive METH misuse.

  7. HUMAN STUDIES

    1. Top of page
    2. REVIEW
    3. BRIEF REPORT: PRECLINICAL STUDIES
    4. PRECLINICAL STUDIES
    5. HUMAN NEUROIMAGING STUDIES
    6. HUMAN NEUROIMAGING STUDISE
    7. BRIEF REPORT: HUMAN STUDY
    8. HUMAN STUDIES
    9. HUMAN GENETIC STUDY
    1. Impaired sleep quality and sleep duration in smokers—results from the German Multicenter Study on Nicotine Dependence (pages 486–496)

      Stefan Cohrs, Andrea Rodenbeck, Dieter Riemann, Bertram Szagun, Andreas Jaehne, Jürgen Brinkmeyer, Gerhard Gründer, Thomas Wienker, Amalia Diaz-Lacava, Arian Mobascher, Norbert Dahmen, Norbert Thuerauf, Johannes Kornhuber, Falk Kiefer, Jürgen Gallinat, Michael Wagner, Dieter Kunz, Ulrike Grittner and Georg Winterer

      Article first published online: 23 AUG 2012 | DOI: 10.1111/j.1369-1600.2012.00487.x

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      Cigarette smoking and sleep disturbance are both severe health burdens being related to several diseases. In a population-based case-control study, significantly more of the 1071 smokers versus 1243 non-smokers (28.1% versus 19.1%; P < 0.0001) demonstrated a disturbed global sleep quality (SQ). After controlling for several confounders, impaired sleep latency, sleep duration and global SQ were significantly more frequent in smokers than non-smokers. It appears likely that smoking is a behaviourally modifiable risk factor for the occurrence of impaired SQ and short sleep duration.

    2. Prefrontal correlates of approach preferences for alcohol stimuli in alcohol dependence (pages 497–508)

      Lena H. Ernst, Michael M. Plichta, Thomas Dresler, Anna K. Zesewitz, Sara V. Tupak, Florian B. Haeussinger, Matthias Fischer, Thomas Polak, Andreas J. Fallgatter and Ann-Christine Ehlis

      Article first published online: 12 NOV 2012 | DOI: 10.1111/adb.12005

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      In an Approach-Avoidance Task, alcohol dependent patients showed stronger behavioural approach preferences for alcohol than non-alcohol stimuli. For non-alcohol stimuli, patients even displayed avoidance preferences. The reversed pattern was found in healthy controls. Group differences in activity of the OFC as measured with functional near-infrared spectroscopy were identical to those in RTs, revealing patients to assign higher subjective value to approaching alcohol stimuli. In both groups, regulatory activity in the right DLPFC was stronger during avoiding than approaching alcohol pictures.

  8. HUMAN GENETIC STUDY

    1. Top of page
    2. REVIEW
    3. BRIEF REPORT: PRECLINICAL STUDIES
    4. PRECLINICAL STUDIES
    5. HUMAN NEUROIMAGING STUDIES
    6. HUMAN NEUROIMAGING STUDISE
    7. BRIEF REPORT: HUMAN STUDY
    8. HUMAN STUDIES
    9. HUMAN GENETIC STUDY
    1. Reduced expression of α-synuclein in alcoholic brain: influence of SNCA-Rep1 genotype (pages 509–515)

      Paulina Janeczek, Rachel K. MacKay, Rodney A. Lea, Peter R. Dodd and Joanne M. Lewohl

      Article first published online: 13 SEP 2012 | DOI: 10.1111/j.1369-1600.2012.00495.x

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      Genetic variability in the α-synuclein gene influences its expression which may contribute to susceptibility to chronic alcohol abuse. Real-time PCR was used to quantify α-synuclein mRNA expression in autopsy samples of human prefrontal cortex. A marker (α-synuclein-repeat 1 microsatellite) associated with expression levels of the gene was genotyped in a Caucasian sample of 126 controls and 117 alcoholics. Alcoholics had greater frequencies of the shortest allele found (267 bp), which was associated with decreased expression of α-synuclein in prefrontal cortex.

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