THE MESOLIMBIC DOPAMINE-ACTIVATING PROPERTIES OF ETHANOL ARE ANTAGONIZED BY MECAMYLAMINE

It has been suggested that ethanol may interact with the central nicot inic acetylcholine receptor, thus providing a basis for the often obse rved high consumption of both ethanol and nicotine. In the present in vivo microdialysis study, ethanol (2.5 g/kg) moderately increased dopa mine overflow in the rat nucleus accumbens. The central nicotinic acet ylcholine receptor antagonist mecamylamine totally counteracted this e ffect in a dose (1.0 mg/kg) that did not alter dopamine overflow per s e. Ethanol also increased the overflow of dihydroxyphenylacetic acid a nd homovanillic acid, but this effect was not altered by mecamylamine (1.0 mg/kg). Furthermore, the ethanol-induced enhancement of 3,4-dihyd roxyphenylalanine accumulation in the mesolimbic dopamine terminal are a after NSD 1015 (an inhibitor of l-aromatic amino acid decarboxylase) was completely antagonized by mecamylamine in doses (3.0 and 6.0 mg/k g) that exerted no effects per se. Neither ethanol nor mecamylamine ch anged the catecholamine synthesis rate in the striatum or the cerebral cortex. These results provide further evidence that ethanol-induced a ctivation of the mesolimbic dopamine system (increased dopamine synthe sis and release) may be mediated via stimulation of central nicotinic acetylcholine receptors. It is suggested that antagonists of central n icotinic acetylcholine receptors may be useful in the treatment of alc oholism.