ETHANOL WITHDRAWAL ENHANCES THE PRODYNORPHIN SYSTEM ACTIVITY IN THE RAT NUCLEUS-ACCUMBENS

The present study investigated the effects of ethanol withdrawal after its chronic administration on endogenous opioid systems in the nucleu s accumbens of rats. An in situ hybridization study showed an increase in the prodynorphin mRNA level at 24 and 48 h (by 189 and 146%, respe ctively) after ethanol withdrawal, whereas the proenkephalin mRNA leve l remained unchanged. Furthermore, after a 48 h withdrawal period, the level of alpha-neoendorphin (alpha NEO), a prodynorphin-derived pepti de, was significantly decreased (by 48%), that effect being associated with the enhancement of the K+-stimulated release of that peptide fro m nucleus accumbens slices. At 96 h after ethanol withdrawal, only the basal release of alpha NEO was elevated, while other parameters retur ned to the control level. Our data indicate that after 48 h of ethanol withdrawal, prodynorphin neurons are highly activated. The increased supply of endogenous kappa opioid receptor agonists in the nucleus acc umbens at that time may promote aversive states during ethanol withdra wal. (C) 1997 Elsevier Science Ireland Ltd.