ACCUMBAL DOPAMINE OVERFLOW AFTER ETHANOL - LOCALIZATION OF THE ANTAGONIZING EFFECT OF MECAMYLAMINE

It has been suggested that ethanol exerts its mesolimbic dopamine acti vating effects and its reinforcing effects via interaction with centra l nicotinic acetylcholine receptors, thus providing a basis for the of ten observed covariation between ethanol and nicotine consumption. We have previously demonstrated that the central nicotinic acetylcholine receptor antagonist mecamylamine totally counteracts the ethanol-induc ed elevation of extracellular dopamine in the nucleus accumbens, as me asured by in vivo microdialysis. A contribution of peripheral nicotini c receptor blockade could, however, not be excluded. In the present st udy, mecamylamine (1.0 mg/kg, i.p.) again totally counteracted the eth anol-induced dopamine overflow, as measured by in vivo microdialysis, while the quarternary nicotinic receptor antagonist hexamethonium (10 mg/kg, i.p.) did not. Furthermore, the increase in accumbal dopamine o verflow after systemic ethanol (2.5 g/kg, i.p.) was counteracted by lo cal perfusion of mecamylamine (50 mu M) in the ipsilateral ventral teg mental area, but not by mecamylamine perfusion in the nucleus accumben s. Ethanol-induced accumbal dopamine overflow was also counteracted by perfusion of hexamethonium (250 mu M) in the ventral tegmental area. These results provide further evidence that ethanol-induced activation of the mesolimbic dopamine system is mediated via stimulation of cent ral nicotinic acetylcholine receptors, and that the receptor populatio n within the ventral tegmental area may be the most important in this regard. It is suggested that antagonists of central nicotinic acetylch oline receptors may be useful in the treatment of alcoholism. (C) 1997 Elsevier Science B.V.