PROFOUND DECREMENT OF MESOLIMBIC DOPAMINERGIC NEURONAL-ACTIVITY DURING ETHANOL WITHDRAWAL SYNDROME IN RATS - ELECTROPHYSIOLOGICAL AND BIOCHEMICAL-EVIDENCE

Activity of the mesolimbic dopaminergic system was investigated in rat s withdrawn from chronic ethanol administration by single-cell extrace llular recordings from dopaminergic neurons of the ventrotegmental are a, coupled with antidromic identification from the nucleus accumbens, and by microdialysis-technique experiments in the nucleus accumbens. S pontaneous firing rates, spikes per burst, and absolute burst firing b ut not the number of spontaneously active neurons were found drastical ly reduced; whereas absolute and relative refractory periods increased in rats withdrawn from chronic ethanol treatment as compared with chr onic saline-treated controls. Consistently, dopamine outflow in the nu cleus accumbens and its acid metabolites were reduced after abruptly s topping chronic ethanol administration. All these changes, as well as ethanol-withdrawal behavioral signs, were reversed by ethanol administ ration. This reversal suggests that the abrupt cessation of chronic et hanol administration plays a causal role in the reduction of mesolimbi c dopaminergic activity seen in the ethanol-withdrawal syndrome. Resul ts indicate that during the ethanol-withdrawal syndrome the mesolimbic dopaminergic system is tonically reduced in activity, as indexed by e lectrophysiological and biochemical criteria. Considering the role of the mesolimbic dopaminergic system in the reinforcing properties of et hanol, the depressed activity of this system during the ethanol-withdr awal syndrome may be relevant to the dysphoric state associated with e thanol withdrawal in humans.