Rapid, Transient Potentiation of Dendritic Spines in Context-Induced Relapse to Cocaine Seeking.

Rapid, transient potentiation of dendritic spines in context-induced relapse to cocaine seeking.

Addict Biol. 2013 May 6;
Stankeviciute NM, Scofield MD, Kalivas PW, Gipson CD

Addiction to cocaine produces long-lasting, stable changes in brain synaptic physiology that might contribute to the vulnerability to relapse. In humans, exposure to environmental contexts previously paired with drug use precipitates relapse, but the neurobiological mechanisms mediating this process are unknown. Initiation of cocaine relapse via re-exposure to a drug-associated context elicited reinstatement of cocaine seeking as well as rapid, transient synaptic plasticity in the nucleus accumbens core (NAcore), measured as an increase in dendritic spine diameter. These results show that rapid context-evoked synaptic potentiation in the NAcore may underpin relapse to cocaine use. HubMed – addiction

Histamine H3 receptors, The complex interaction with dopamine and its implications for addiction.

Br J Pharmacol. 2013 May 3;
Ellenbroek BA

Histamine H3 receptors are best known as presynaptic receptors inhibiting the release of histamine, as well as other neurotransmitters including acetylcholine and dopamine. However, in the dorsal and ventral striatum, the vast majority of H3 receptors are actually located postsynaptically on medium sized spiny output neurons. These cells also contain large numbers of dopamine (D1 and D2) receptors and it has been shown that H3 receptors form heterodimers with both dopamine receptors. Thus the anatomical localization of H3 receptors suggests a complex interaction that could both enhance and inhibit the dopaminergic neurotransmission. Dopamine especially within the striatal complex plays a crucial role in the development of addiction, both in the initial reinforcing effects of drugs of abuse, as well as in maintenance, relapse and reinstatement of drug taking behaviour. It is therefore conceivable that H3 receptors can moderate the development and maintenance of drug addiction. In the present paper, we will review the current literature on the involvement of H3 receptors in drug addiction and will try to explain these data in a theoretical framework, as well as provide suggestions for further research. HubMed – addiction

Impact of Lifetime Alcohol Use on Liver Fibrosis in a Population of HIV-Infected Patients With and Without Hepatitis C Coinfection.

Alcohol Clin Exp Res. 2013 May 3;
Fuster D, Tsui JI, Cheng DM, Quinn EK, Bridden C, Nunes D, Libman H, Saitz R, Samet JH

BACKGROUND: The effect of alcohol on liver disease in HIV infection has not been well characterized. METHODS: We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, “FIB-4,” which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index (“APRI”), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg). RESULTS: Subjects (n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus (HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm(3) . Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis (FIB-4 <1.45) (adjusted odds ratio [AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis (FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection. CONCLUSIONS: In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population. HubMed – addiction

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