SYSTEMIC NICOTINE-INDUCED DOPAMINE RELEASE IN THE RAT NUCLEUS-ACCUMBENS IS REGULATED BY NICOTINIC RECEPTORS IN THE VENTRAL TEGMENTAL AREA

Stimulation of the mesolimbic dopamine (DA) system is considered of ma jor importance for the rewarding and dependence producing properties o f nicotine (NIC). To identify the site of this stimulatory action, sim ultaneous microdialysis was performed in the ventral tegmental area (V TA) and the ipsilateral nucleus accumbens (NAC) of awake rats. Extrace llular concentrations of DA and its metabolites were measured in the N AC. NIC (0.5 mg/kg, s.c.) increased DA and its metabolites by similar to 50%. Concomitant infusion of the nicotinic receptor antagonist meca mylamine (MEC, 100 mu M) through the VTA probe, starting 40 min before NIC injection, antagonized the NIC induced increases of DA and its me tabolites. In contrast, similar MEC pretreatment (40 or 140 min) in th e NAC did not affect DA or metabolite responses to systemic NIC. Infus ion of NIC (1,000 mu M) in the NAC or the VTA increased DA release by 49% and 48%, respectively, whereas only the VTA infusion increased met abolite concentrations by similar to 25%. MEC infusion (1-1,000 mu M) in the VTA did not affect DA or its metabolites, whereas the 1,000 mu M concentration infused in the NAC increased DA by 77%. These results suggest that nicotinic receptors in the somatodendritic region may be of greater importance than those located in the terminal area for the stimulatory action of systemic NIC on the mesolimbic DA system. Furthe rmore, our findings support the notion that the mesolimbic dopaminergi c system is phasically rather than tonically regulated by nicotinic re ceptor activation within the VTA. (C) 1994 Wiley-Liss, Inc.