PubMed · 5689696
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
1968-05-31. Alcoholic units.. https://pubmed.ncbi.nlm.nih.gov/5689696/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Biochemical and pharmacological evidence suggest that the dopaminergic mesolimbic system plays a key role in mediating the reinforcing properties of alcohol and other drugs of abuse. Alcohol reinforcement and high alcohol drinking behavior have been postulated to be partially mediated by a neurobiological mechanism involving the alcohol-induced activation of the endogenous opioid system. The aim of this work was to study the effect of the in vivo acute administration of ethanol on mu (mu) opioid receptors in the rat dopaminergic meso-accumbens and mesocortical pathways by quantitative receptor autoradiography. [(3)H]DAMGO binding was significantly decreased in the ventral tegmental area (VTA) 30 min after ethanol administration. A small ethanol-induced reduction was observed in the shell region of the nucleus accumbens 1 h after exposure. In contrast, 2 h after ethanol administration, [(3)H]DAMGO binding was significantly increased in the frontal and prefrontal cortices. The observed changes correlated well with high ethanol plasma levels. Our results suggest that the reinforcing properties of ethanol may be partially mediated by mechanisms involving the ethanol-induced down- and up-regulation of mu receptors in the dopaminergic mesolimbic system. Mu receptors in the VTA and the frontal and prefrontal cortices may be involved in the in vivo acute responses to ethanol and could play a key role in modulating the dopaminergic activity of the mesocortical pathway in response to the drug. In contrast, the contribution of both mu and delta receptors in the nucleus accumbens might be relevant in these processes.
A higher proportion of alcoholics than non-alcoholics smoke (>80 vs 30%). In animals, chronic administration of alcohol induces tolerance to some effects of nicotine. To investigate if chronic ethanol (EtOH) induces alterations in CYP2B1/2 and nicotine C-oxidation activity, male rats (N = 4-6/group) were treated once daily with saline or EtOH (0.3, 1.0, and 3.0 g/kg, p.o./by gavage) for 7 days. A quantitative immunoblotting assay was developed to detect CYP2B1/2 in the brain, where constitutive expression is low, and in the liver. Using this method, it was determined that EtOH did not alter CYP2B1/2 protein expression significantly in six brain regions (olfactory bulbs, olfactory tubercles, frontal cortex, hippocampus, cerebellum, and brainstem). However, a dose-dependent induction of CYP2B1/2 protein expression was detected in the liver. Significant induction of 2-, 3-, and 2.7-fold were observed for the 0.3, 1.0, and 3.0 g/kg doses, respectively. Increases were also observed in CYP2B1 mRNA, which was induced by 14, 38, and 43% at the same doses. Liver microsomal nicotine C-oxidation also was increased (1.3 to 4.5-fold). CYP2B selective inactivators demonstrated that approximately 70% of nicotine C-oxidation was mediated by CYP2B1/2 in both EtOH-induced and uninduced hepatic microsomes. In summary, chronic, behaviorally relevant doses of EtOH induce CYP2B1/2 protein, mRNA, and nicotine C-oxidation activity in rat liver but not in rat brain, and these increases could contribute to cross-tolerance and co-abuse of ethanol and nicotine.