Acute nicotine injections induce c-fos mostly in non-dopaminergic neurons of the midbrain of the rat.

Induction of c-fos gene is an immediate and early response in the cascade of molecular events that ultimately lead to long-term alterations in gene expression in neurons. The psychomotor stimulant and positive reinforcing effects of nicotine have been speculated to be mediated by the dopaminergic neurons of the ventral tegmental area (VTA). To identify the precise subsets of VTA neurons of the rat that mediate the acute nicotinergic effects, the pattern of expression of c-fos gene was mapped using immunocytochemical methods. Acute nicotine injections resulted in prominent Fos-like immunoreactivity (-LI) in the medial terminal nucleus of the accessory optic system, the interpeduncular nucleus, and in the caudal linear subnucleus of VTA. The neurons of other VTA subnuclei, viz., the rostral linear, paranigralis, nucleus parabrachialis pigmentosus, and nucleus interfascicularis or the substantia nigra pars compacta did not contain any cells with Fos-LI. Mecamylamine abolished Fos-LI in most of the VTA neurons. These results suggest that acute nicotine injections induce c-fos expression mostly in non-dopaminergic neurons of the ventral tegmental area of the rat and that nicotine induces c-fos most intensely in the interpeduncular nucleus, the superior colliculus, and several other subnuclei of the accessory optic system.