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The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [11 C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals. [ABSTRACT FROM AUTHOR]

Abstract: Cigarette smoking presents a significant worldwide healthcare challenge. Preclinical, genetic association and clinical trials studies provide considerable evidence for the involvement of the human γ-aminobutyric acid (GABA) system in the neurobiology of nicotine addiction. However there are few human GABA neurochemical imaging studies of nicotine addiction. We investigated limbic GABAA receptor availability in volunteers with a history of cigarette smoking using [11C]Ro15 4513 positron emission tomography (PET). Eight [11C]Ro15 4513 PET scans from volunteers with a history of cigarette smoking were compared to twelve scans from volunteers who were non-smokers. Total, α1 and α5 GABAA receptor subtype [11C]Ro15 4513 VT values were quantified using spectral analysis of limbic regions implicated in nicotine addiction. Spectral analysis allows quantification of the overall [11C]Ro15 4513 spectral frequency as well as α1 and α5 GABAA receptor subtype specific spectral frequency components. Volunteers with a history of cigarette smoking showed significantly higher total [11C]Ro15 4513 VT values in the presubgenual cingulate and parahippocampal gyrus, and at a trend level in the insula, nucleus accumbens and subgenual cingulate. In six abstinent previous smokers (‘ex-smokers’), total [11C]Ro15 4513 binding was significantly higher in all limbic regions studied, with higher α5 availability in the amygdala, anterior cingulate, nucleus accumbens and presubgenual cingulate. These results suggest that limbic GABAA receptor availability is higher in volunteers with a history of cigarette smoking which may reflect either higher expression of GABAA receptors or lower endogenous GABA levels. The findings in ex-smokers suggest that higher GABAA receptor availability continues with abstinence indicating that this may be a trait marker for nicotine addiction or that alterations in GABA function associated with cigarette smoking persist. [Copyright &y& Elsevier]

Abstract: Pathological gambling (PG) is a behavioural addiction associated with elevated impulsivity and suspected dopamine dysregulation. Reduced striatal dopamine D2/D3 receptor availability has been reported in drug addiction, and may constitute a premorbid vulnerability marker for addictive disorders. The aim of the present study was to assess striatal dopamine D2/D3 receptor availability in PG, and its association with trait impulsivity. Males with PG (n=9) and male healthy controls (n=9) underwent [11C]-raclopride positron emission tomography imaging and completed the UPPS-P impulsivity scale. There was no significant difference between groups in striatal dopamine D2/D3 receptor availability, in contrast to previous reports in drug addiction. However, mood-related impulsivity (‘Urgency’) was negatively correlated with [11C]-raclopride binding potentials in the PG group. The absence of a group difference in striatal dopamine binding implies a distinction between behavioural addictions and drug addictions. Nevertheless, our data indicate heterogeneity in dopamine receptor availability in disordered gambling, such that individuals with high mood-related impulsivity may show differential benefits from dopamine-based medications. [Copyright &y& Elsevier]