The mesocorticolimbic
dopamine system is believed to be involved in mediating the positive reinforcing effects of drugs of abuse, including
ethanol. The
nicotinic acetylcholine receptor antagonist
mecamylamine perfused via reversed microdialysis in the ventral tegmental area antagonizes the increase of accumbal extracellular
dopamine levels after systemic
ethanol, and, after systemic injection, lowers
ethanol intake in the rat. In the present study the effect of ventral tegmental
mecamylamine on
ethanol intake and preference, as well as on extracellular accumbal
dopamine levels, was investigated in the same animal. To this end, in vivo microdialysis using a double probe approach (one in the nucleus accumbens and one in the ventral tegmental area) was combined with an
ethanol preference model invoking a free choice between a bottle of water and a bottle of
ethanol 6% (v/v)
solution. Wistar rats drinking more than 60% of their total daily fluid intake from the
ethanol solution (
ethanol high-preferring animals) were selected during a screening period and used for the experiments. The animals received vehicle or
mecamylamine (100 microM) in the ventral tegmental area and were then presented with a choice between water and
ethanol in a limited access paradigm to which they previously had been adapted. On the next day the rats that received vehicle day 1 now received
mecamylamine, and vice versa. When treated with vehicle,
ethanol intake and preference were unaltered, as compared to baseline behavior, and accumbal
dopamine levels increased significantly to approximately 130% of the pre-
drug baseline level. When receiving
mecamylamine,
ethanol intake and preference were reduced markedly and
dopamine levels were unaltered, as compared to pre-
drug baseline levels. The present results further indicate that
nicotinic acetylcholine receptors in the ventral tegmental area are involved in the positive reinforcing effects of
ethanol. Thus,
mecamylamine or other antagonists specifically aimed at ventral tegmental
nicotinic acetylcholine receptors could represent a new pharmacological treatment principle against
alcohol abuse, the efficacy of which should be explored in high-scale alcohol consumers or alcoholics.