NICOTINE INJECTIONS INTO THE VENTRAL TEGMENTAL AREA INCREASE LOCOMOTION AND FOS-LIKE IMMUNOREACTIVITY IN THE NUCLEUS-ACCUMBENS OF THE RAT

Systemic administration of nicotine has been shown to increase locomot or activity in rats, an effect which is enhanced by chronic pretreatme nt with the drug. Furthermore, administration of nicotine either syste mically, or locally within the ventral tegmental area (VTA), increases extracellular levels of dopamine (DA) in the nucleus accumbens (NAc). In the present study, we examined the effect of local, bilateral inje ctions into the VTA of nicotine (0.02, 0.2, 2.0 and 8.0 mu g/0.5 mu l/ side) on locomotor activity of rats in an open field. Nicotine (8.0 mu g/side) significantly increased forward locomotion within 20 min afte r injection, whereas rearing was not affected. The stimulatory effect of locally applied nicotine was completely blocked by pretreatment wit h mecamylamine (1.0 mg/kg, s.c.). Repeated intra-tegmental injections of a subthreshold dose of nicotine (2.0 mu g/side every 2 days), gradu ally increased locomotion, compared to the effect of acute intra-tegme ntal administration or control injections of saline, after the fifth a nd sixth injection. The effects of intra-tegmental injections of nicot ine were further investigated on cells in several target areas for the VTA-DA neurons through determination of c-fos expression by means of Fos immunohistochemistry. Intra-tegmental injections of nicotine (8.0 mu g/side) increased Fos-like immunoreactivity in the NAc, but did not affect the number of Fos-positive nuclei in the medial prefrontal cor tex or in the dorsolateral striatum. The increase in accumbal Fos-like immunoreactivity was attenuated by pretreatment with mecamylamine (1. 0 mg/kg, s.c.). Our data demonstrate that locomotor activating effects similar to those evoked by systemically administered nicotine, includ ing behavioral sensitization, can be produced by intra-tegmental nicot ine administration. Moreover, such local VTA administration of the dru g was found to significantly affect neurons within DA target areas. Ou r findings support the notion that the effects of systemically adminis tered nicotine in mesolimbic target areas are largely dependent on sti mulation of nicotinic receptors in the VTA.