Addiction Rehab: The ?7nACh-NMDA Receptor Complex Is Involved in Cue-Induced Reinstatement of Nicotine Seeking.
The ?7nACh-NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking.
Filed under: Addiction Rehab
J Exp Med. 2012 Oct 22;
Li S, Li Z, Pei L, Le AD, Liu F
Smoking is the leading preventable cause of disease, disability, and premature death. Nicotine, the main psychoactive drug in tobacco, is one of the most heavily used addictive substances, and its continued use is driven through activation of nicotinic acetylcholine receptors (nAChRs). Despite harmful consequences, it is difficult to quit smoking because of its positive effects on mood and cognition that are strong reinforcers contributing to addiction. Furthermore, a formidable challenge for the treatment of nicotine addiction is the high vulnerability to relapse after abstinence. There is no currently available smoking cessation product able to achieve a >20% smoking cessation rate after 52 wk, and there are no medications that directly target the relapse process. We report here that the ?7nAChR forms a protein complex with the NMDA glutamate receptor (NMDAR) through a direct protein-protein interaction. Chronic nicotine exposure promotes ?7nAChR-NMDAR complex formation. Interestingly, administration of an interfering peptide that disrupts the ?7nAChR-NMDAR complex decreased extracellular signal-regulated kinase (ERK) activity and blocked cue-induced reinstatement of nicotine seeking in rat models of relapse, without affecting nicotine self-administration or locomotor activity. Our results may provide a novel therapeutic target for the development of medications for preventing nicotine relapse.
HubMed – addiction
A quasi-randomized group trial of a brief alcohol intervention on risky single occasion drinking among secondary school students.
Filed under: Addiction Rehab
Int J Public Health. 2012 Oct 23;
Gmel G, Venzin V, Marmet K, Danko G, Labhart F
OBJECTIVES: To show the effectiveness of a brief group alcohol intervention. Aims of the intervention were to reduce the frequency of heavy drinking occasions, maximum number of drinks on an occasion and overall weekly consumption. METHODS: A cluster quasi-randomized control trial (intervention n = 338; control n = 330) among 16- to 18-year-old secondary school students in the Swiss Canton of Zürich. Groups homogeneous for heavy drinking occasions (5+/4+ drinks for men/women) consisted of those having medium risk (3-4) or high risk (5+) occasions in the past 30 days. Groups of 8-10 individuals received two 45-min sessions based on motivational interviewing techniques. RESULTS: Borderline significant beneficial effects (p < 0.10) on heavy drinking occasions and alcohol volume were found 6 months later for the medium-risk group only, but not for the high-risk group. None of the effects remained significant after Bonferroni corrections. CONCLUSIONS: Group intervention was ineffective for all at-risk users. The heaviest drinkers may need more intensive treatment. Alternative explanations were iatrogenic effects among the heaviest drinkers, assessment reactivity, or reduction of social desirability bias at follow-up through peer feedback. HubMed – addiction
A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.
Filed under: Addiction Rehab
Mol Psychiatry. 2012 Oct 23;
Wang JC, Foroud T, Hinrichs AL, Le NX, Bertelsen S, Budde JP, Harari O, Koller DL, Wetherill L, Agrawal A, Almasy L, Brooks AI, Bucholz K, Dick D, Hesselbrock V, Johnson EO, Kang S, Kapoor M, Kramer J, Kuperman S, Madden PA, Manz N, Martin NG, McClintick JN, Montgomery GW, Nurnberger JI, Rangaswamy M, Rice J, Schuckit M, Tischfield JA, Whitfield JB, Xuei X, Porjesz B, Heath AC, Edenberg HJ, Bierut LJ, Goate AM
Several studies have identified genes associated with alcohol-use disorders (AUDs), but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol-dependence symptom counts (P=4.5 × 10(-8), inflation-corrected P=9.4 × 10(-7)). Results with DSM-IV AD in the regions of interest support our findings with SC, although the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: nonoverlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian Twin Family Study of AUDs (OZALC). Nominal association of C15orf53 with SC was observed in SAGE. The variant that showed strongest association with SC, rs12912251 and its highly correlated variants (D’=1, r(2)? 0.95), have previously been associated with risk for bipolar disorder.Molecular Psychiatry advance online publication, 23 October 2012; doi:10.1038/mp.2012.143.
HubMed – addiction
Early relapse in alcohol dependence may result from late withdrawal symptoms.
Filed under: Addiction Rehab
Med Hypotheses. 2012 Oct 19;
Simioni N, Cottencin O, Guardia D, Rolland B
Alcohol dependence has two distinct clinical features: (1) Physiological Dependence (PD), which characterizes the pharmacological tolerance that alcohol progressively induces in the brain and (2) Alcohol Addiction (AA), which is the behavioral conditioning of alcohol drinking resulting from the chronic activation of the reward system. PD results from a progressive imbalance between excitatory and inhibitory neurotransmission systems and leads to the occurrence of Alcohol Withdrawal Syndrome (AWS), which is prevented by benzodiazepines in cases of alcohol cessation. AA is considered to persist much longer and results from a disruption of the dopaminergic mesolimbic pathway, which is treated by anticraving drugs. Relapse in alcohol dependence is usually considered to be the result of AA. However, 50% of the relapses in alcohol occur within the first month after alcohol cessation. During this period, it has been shown that many patients experience anxious symptoms that have been neurobiologically related to withdrawal symptoms and PD. Thus, we hypothesize that early relapses are more the consequence of late symptoms of PD than AA. From this standpoint, we propose that prolonged treatment with benzodiazepines may reduce the first-month relapse rate.
HubMed – addiction
Find More Addiction Rehab Information…