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.