Acetaldehyde as a Drug of Abuse: Insight Into AM281 Administration on Operant-Conflict Paradigm in Rats.

Acetaldehyde as a drug of abuse: insight into AM281 administration on operant-conflict paradigm in rats.

Front Behav Neurosci. 2013; 7: 64
Plescia F, Brancato A, Marino RA, Cannizzaro C

Increasing evidence focuses on acetaldehyde (ACD) as the mediator of the rewarding and motivational properties of ethanol. Indeed, ACD stimulates dopamine release in the nucleus accumbens and it is self-administered under different conditions. Besides the dopaminergic transmission, the endocannabinoid system has been reported to play an important role in ethanol central effects, modulating primary alcohol rewarding effect, drug-seeking, and relapse behavior. Drug motivational properties are highlighted in operant paradigms which include response-contingent punishment, a behavioral equivalent of compulsive drug use despite adverse consequences. The aim of this study was thus to characterize ACD motivational and rewarding properties employing an operant-conflict paradigm in which rats, trained to lever press in order to get ACD solution (0.9%), undergo extinction, reinstatement and conflict sessions, according to a modified Geller-Seifter procedure. Furthermore, the role played by CB1 receptor system in modulating ACD-induced effects were investigated through the administration of CB1 receptor antagonist, AM281 (1 mg/kg, i.p.) during the extinction-, relapse-, and conflict-experiments. Our results indicate that ACD is able to induce and maintain an operant behavior, a high number of responses during extinction, an increase in the lever presses during the reinstatement phase, and a higher emission of punished responses during the conflict experiments, when compared to controls. The administration of AM281 is able to decrease ACD-seeking behavior during extinction, the number of lever presses during reinstatement and to strongly decrease the punished responses for ACD. Our data strengthen the idea that ACD may be responsible for the central effects of ethanol, and pinpoint at the CB1 system as one of the neural substrates underlying its addictive properties. HubMed – addiction

The hypocretins and the reward function: what have we learned so far?

Front Behav Neurosci. 2013; 7: 59
Boutrel B, Steiner N, Halfon O

A general consensus acknowledges that drug consumption (including alcohol, tobacco, and illicit drugs) constitutes the leading cause of preventable death worldwide. But the global burden of drug abuse extends the mortality statistics. Indeed, the comorbid long-term debilitating effects of the disease also significantly deteriorate the quality of life of individuals suffering from addiction disorders. Despite the large body of evidence delineating the cellular and molecular adaptations induced by chronic drug consumption, the brain mechanisms responsible for drug craving and relapse remain insufficiently understood, and even the most recent developments in the field have not brought significant improvement in the management of drug dependence. Though, recent preclinical evidence suggests that disrupting the hypocretin (orexin) system may serve as an anticraving medication therapy. Here, we discuss how the hypocretins, which orchestrate normal wakefulness, metabolic health and the execution of goal-oriented behaviors, may be compromised and contribute to elicit compulsive drug seeking. We propose an overview on the most recent studies demonstrating an important role for the hypocretin neuropeptide system in the regulation of drug reward and the prevention of drug relapse, and we question the relevance of disrupting the hypocretin system to alleviate symptoms of drug addiction. HubMed – addiction

Robust Changes in Reward Circuitry During Reward Loss in Current and Former Cocaine Users During Performance of a Monetary Incentive Delay Task.

Biol Psychiatry. 2013 Jun 15;
Patel KT, Stevens MC, Meda SA, Muska C, Thomas AD, Potenza MN, Pearlson GD

BACKGROUND: Abnormal function in reward circuitry in cocaine addiction could predate drug use as a risk factor, follow drug use as a consequence of substance-induced alterations, or both. METHODS: We used a functional magnetic resonance imaging monetary incentive delay task (MIDT) to investigate reward-loss neural response differences among 42 current cocaine users, 35 former cocaine users and 47 healthy subjects who also completed psychological measures and tasks related to impulsivity and reward. RESULTS: We found various reward processing-related group differences in several MIDT phases. Across task phases we found a control > current user > former user activation pattern, except for loss outcome, where former compared with current cocaine users activated ventral tegmental area more robustly. We also found regional prefrontal activation differences during loss anticipation between cocaine-using groups. Both groups of cocaine users scored higher than control subjects on impulsivity, compulsivity and reward-punishment sensitivity factors. In addition, impulsivity-related factors correlated positively with activation in amygdala and negatively with anterior cingulate activation during loss anticipation. CONCLUSIONS: Compared with healthy subjects, both former and current users displayed abnormal brain activation patterns during MIDT performance. Both cocaine groups differed similarly from healthy subjects, but differences between former and current users were localized to the ventral tegmental area during loss outcome and to prefrontal regions during loss anticipation, suggesting that long-term cocaine abstinence does not normalize most reward circuit abnormalities. Elevated impulsivity-related factors that relate to loss processing in current and former users suggest that these tendencies and relationships may pre-exist cocaine addiction. HubMed – addiction

New definition of addiction proposed by the American Society of Addiction Medicine: Which implications for the treatment of tobacco dependence?

Eur Neuropsychopharmacol. 2013 Jun 15;
Caraci F, Drago F

HubMed – addiction

The longitudinal association between social functioning and theory of mind in first-episode psychosis.

Cogn Neuropsychiatry. 2013 Jun 18;
Sullivan S, Lewis G, Mohr C, Herzig D, Corcoran R, Drake R, Evans J

Introduction. There is some cross-sectional evidence that theory of mind ability is associated with social functioning in those with psychosis but the direction of this relationship is unknown. This study investigates the longitudinal association between both theory of mind and psychotic symptoms and social functioning outcome in first-episode psychosis. Methods. Fifty-four people with first-episode psychosis were followed up at 6 and 12 months. Random effects regression models were used to estimate the stability of theory of mind over time and the association between baseline theory of mind and psychotic symptoms and social functioning outcome. Results. Neither baseline theory of mind ability (regression coefficients: Hinting test 1.07 95% CI -0.74, 2.88; Visual Cartoon test -2.91 95% CI -7.32, 1.51) nor baseline symptoms (regression coefficients: positive symptoms -0.04 95% CI -1.24, 1.16; selected negative symptoms -0.15 95% CI -2.63, 2.32) were associated with social functioning outcome. There was evidence that theory of mind ability was stable over time, (regression coefficients: Hinting test 5.92 95% CI -6.66, 8.92; Visual Cartoon test score 0.13 95% CI -0.17, 0.44). Conclusions. Neither baseline theory of mind ability nor psychotic symptoms are associated with social functioning outcome. Further longitudinal work is needed to understand the origin of social functioning deficits in psychosis. HubMed – addiction