ABSTRACT

Dopaminergic mesolimbic neurons in the brain, with cell bodies in the ventral tegmental area (VTA) projecting to terminals in the nucleus accumbens (NAc), have been shown to be intimately involved in the development of drug dependence. The application of nicotine to either the VTA or NAc produces an increase in dopamine release from the terminals of these neurons, however dopamine release and positive reinforcement produced by the systemic injection of nicotine has been found to be primarily a result of the stimulation of nicotinic acetylcholine receptors (nAChRs) in the VTA rather than the NAc. Because the brain levels of nicotine would likely be the same in both brain areas, the nAChRs in the NAc may be less sensitive than those in the VTA. This study was undertaken to make a direct comparison of the native nAChRs in intact slices of NAc and VTA by measuring nicotine-stimulated efflux of ⁸⁶Rb⁺ in a superfusion assay. The potency of nicotine and several other agonists was similar in both brain areas, but nicotine was somewhat more efficacious in the NAc. The effects of treatment duration, calcium and nicotinic antagonist were also determined. The results suggest that the predominant effect of nicotine in the VTA rather than the NAc following systemic administration is due to differences in neuronal circuitry or firing patterns rather than inherent differences in the nAChR populations between the two brain areas.