Addiction Rehab: Increased Vulnerability to Cocaine in Mice Lacking Dopamine D3 Receptors.

Increased vulnerability to cocaine in mice lacking dopamine D3 receptors.

Filed under: Addiction Rehab

Proc Natl Acad Sci U S A. 2012 Oct 8;
Song R, Zhang HY, Li X, Bi GH, Gardner EL, Xi ZX

Neuroimaging studies using positron emission tomography suggest that reduced dopamine D(2) receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D(3) receptors (D(3)Rs) in the neurobiology of addiction remains unclear, however. Here we report that D(3)R KO (D(3)(-/-)) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D(3)(-/-) mice. In addition, D(3)(-/-) mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadaptative attempt to normalize elevated basal extracellular dopamine. These findings suggest that D(3)R deletion increases vulnerability to cocaine, and that reduced D(3)R availability in the brain may constitute a risk factor for the development of cocaine addiction.
HubMed – addiction


Dopamine receptor D1 and postsynaptic density gene variants associate with opiate abuse and striatal expression levels.

Filed under: Addiction Rehab

Mol Psychiatry. 2012 Oct 9;
Jacobs MM, Okvist A, Horvath M, Keller E, Bannon MJ, Morgello S, Hurd YL

Opioid drugs are highly addictive and their abuse has a strong genetic load. Dopamine-glutamate interactions are hypothesized to be important for regulating neural systems central for addiction vulnerability. Balanced dopamine-glutamate interaction is mediated through several functional associations, including a physical link between discs, large homolog 4 (Drosophila) (DLG4, PSD-95) and dopamine receptor 1 (DRD1) within the postsynaptic density to regulate DRD1 trafficking. To address whether genetic associations with heroin abuse exist in relation to dopamine and glutamate and their potential interactions, we evaluated single-nucleotide polymorphisms of key genes within these systems in three populations of opiate abusers and controls, totaling 489 individuals from Europe and the United States. Despite significant differences in racial makeup of the separate samples, polymorphisms of DRD1 and DLG4 were found to be associated with opiate abuse. In addition, a strong gene-gene interaction between homer 1 homolog (Drosophila) (HOMER1) and DRD1 was predicted to occur in Caucasian subjects. This interaction was further analyzed by evaluating DRD1 genotype in relation to HOMER1b/c protein expression in postmortem tissue from a subset of Caucasian subjects. DRD1 rs265973 genotype correlated with HOMER1b/c levels in the striatum, but not cortex or amygdala; the correlation was inversed in opiate abusers as compared with controls. Cumulatively, these results support the hypothesis that there may be significant, genetically influenced interactions between glutamatergic and dopaminergic pathways in opiate abusers.Molecular Psychiatry advance online publication, 9 October 2012; doi:10.1038/mp.2012.140.
HubMed – addiction


Dual Roles of Dopamine in Food and Drug Seeking: The Drive-Reward Paradox.

Filed under: Addiction Rehab

Biol Psychiatry. 2012 Oct 5;
Wise RA

The question of whether (or to what degree) obesity reflects addiction to high-energy foods often narrows to the question of whether the overeating of these foods causes the same long-term neuroadaptations as are identified with the late stages of addiction. Of equal or perhaps greater interest is the question of whether common brain mechanisms mediate the acquisition and development of eating and drug-taking habits. The earliest evidence on this question is rooted in early studies of brain stimulation reward. Lateral hypothalamic electrical stimulation can be reinforcing in some conditions and can motivate feeding in others. That stimulation of the same brain region should be both reinforcing and drive inducing is paradoxical; why should an animal work to induce a drive-like state such as hunger? This is known as the drive-reward paradox. Insights into the substrates of the drive-reward paradox suggest an answer to the controversial question of whether the dopamine system-a system downstream from the stimulated fibers of the lateral hypothalamus-is more critically involved in wanting or in liking of various rewards including food and addictive drugs. That the same brain circuitry is implicated in the motivation for and the reinforcement by both food and addictive drugs extends the argument for a common mechanism underlying compulsive overeating and compulsive drug taking.
HubMed – addiction


Treatment outcome and its predictors among Asian problem drinkers.

Filed under: Addiction Rehab

Drug Alcohol Rev. 2012 Oct 9;
Manning V, Gomez B, Koh PK, Ng A, Guo S, Kandasami G, Wong KE

INTRODUCTION AND AIMS: Evidence of treatment effectiveness for alcohol use disorders (AUD) have emerged predominantly from Western studies, using highly controlled trials that may not reflect real-world settings. This paper examines treatment outcome and its predictors among Asian problem drinkers participating in a treatment outcome monitoring program at an addiction treatment centre in Singapore. DESIGN AND METHODS: Data were collected at intake and 3, 6 and 12 months, although the focus of this paper is on reliable change at 3 months among the 70% who were followed up. Five hundred and forty-one AUD-diagnosed outpatients presenting for treatment, over a 2-year period, were assessed on drinking behaviours and administered the Addiction Severity Index-Lite, Personal Wellbeing Index (PWI) and Treatment Perceptions Questionnaire. RESULTS: At 3 months, drinking days, alcohol units and alcohol use severity had more than halved and 69% were either abstinent or had reliably reduced their drinking days. Baseline drinking days and treatment satisfaction predicted 3-month drinking frequency but not severity. Positive alcohol outcomes observed at 3 months were sustained among those followed up until 12 months. Mean PWI score improved significantly and fell within the ‘normal’ range. Treatment satisfaction also emerged as the only significant predictor of reliable positive change in both drinking days and PWI score. DISCUSSION AND CONCLUSIONS: Significant reductions in drinking frequency and severity are possible for Asian problem drinkers after 12 weeks of outpatient treatment. The identified predictors suggest that more frequent drinkers and patients with past/current psychiatric comorbidities may require a more intensive treatment approach to optimise treatment outcomes.
HubMed – addiction



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