MESOLIMBIC DOPAMINERGIC REDUCTION OUTLASTS ETHANOL WITHDRAWAL SYNDROME - EVIDENCE OF PROTRACTED ABSTINENCE

Rats chronically administered with ethanol every six hours for six con secutive days show, upon suspension of treatment, a marked somatic wit hdrawal syndrome characterized by classical neurological signs. The em ergence of the behavioral syndrome coincides with a profound decline o f dopaminergic mesolimbic neuronal activity which corresponds to a red uction of dopamine outflow in the nucleus accumbens [Diana ct al. (199 3) Proc. natn. Acad. Sci. U.S.A. 90, 7966-7969]. However, while the be havioral manifestation of the ethanol withdrawal syndrome recedes in a bout 48 h, electrophysiological indices of mesolimbic dopaminergic fun ction are still reduced 72 h after ethanol discontinuation, thus outla sting the physical signs of ethanol withdrawal syndrome. Dopaminergic neuronal activity is reintegrated by anti-craving drugs such as ethano l itself and gamma-hydroxybutyric acid. It is postulated that the redu ced spontaneous activity of mesolimbic dopaminergic neurons may form t he neural basis of the dysphoric state which accompanies abrupt interr uption of chronic ethanol administration. Pharmacological manipulation s of dopaminergic activity targeted at restoring ''normal'' dopaminerg ic function after ethanol withdrawal may lead to way to the experiment al basis of new therapeutic strategies of alcoholism.