NICOTINE AND FOOD-INDUCED DOPAMINE RELEASE IN THE NUCLEUS-ACCUMBENS OF THE RAT - PUTATIVE ROLE OF ALPHA-7 NICOTINIC RECEPTORS IN THE VENTRAL TEGMENTAL AREA

We have recently shown that the stimulatory effect of nicotine on dopa mine output in the nucleus accumbens is largely dependent upon an enha nced glutamate transmission via N-methyl-D-aspartate receptors, possib ly through stimulation of nicotinic receptors localized presynapticall y on glutamatergic afferents in the ventral tegmental area, Given that nicotinic alpha 7 receptors have been proposed to be involved in pres ynaptic regulation of glutamate release, we investigated whether alpha 7 receptors underlie such a mechanism in the ventral tegmental area. For this purpose, by utilizing microdialysis we measured dopamine rele ase in the nucleus accumbens in response to systemic nicotine, with, o r without, concomitant infusion into the ventral tegmental area of the selective alpha 7 receptor antagonist methyllycaconitine. To test als o whether alpha 7 nicotinic receptor antagonism within the ventral teg mental area affected a natural reward-mediated increase in dopamine re lease in the nucleus accumbens, me employed a model of schedule-induce d feeding. Intrategmental administration of methyl-lycaconitine decrea sed both the nicotine-induced and the food-induced dopamine release in the nucleus accumbens. We suggest that alpha 7 nicotinic receptors in the ventral tegmental area are involved in the acute effect of nicoti ne on dopamine release in the nucleus accumbens and conclude that the mechanism, by which nicotine stimulates the mesolimbic dopaminergic sy stem, may be an essential constituent of the natural reward-related ci rcuits in brain. (C) 1998 IBRO. Published by Elsevier Science Ltd.