Acute ethanol administration differentially modulates mu opioid receptors in the rat meso-accumbens and mesocortical pathways

Biochemical and pharmacological evidence suggest that the dopaminergic meso limbic system plays a key role in mediating the reinforcing properties of a lcohol and other drugs of abuse. Alcohol reinforcement and high alcohol dri nking behavior have been postulated to be partially mediated by a neurobiol ogical 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 dop aminergic meso-accumbens and mesocortical pathways by quantitative receptor auto radiography. [H-3]DAMGO binding was significantly decreased in the ve ntral tegmental area (VTA) 30 min after ethanol administration. A small eth anol-induced reduction was observed in the shell region of the nucleus accu mbens 1 It after exposure. In contrast, 2 h after ethanol administration, [ H-3]DAMGO binding was significantly increased in the frontal and prefrontal cortices. The observed changes correlated well with high ethanol plasma le vels. Our results suggest that the reinforcing properties of ethanol may be partially mediated by mechanisms involving the ethanol-induced down- and u p-regulation of L receptors in the dopaminergic mesolimbic system. Mu recep tors 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 modulat ing the dopaminergic activity of the mesocortical pathway in response to th e drug. In contrast, the contribution of both mu and 8 receptors in the nuc leus accumbens might be relevant in these processes. (C) 2001 Elsevier Scie nce BY All rights reserved.