Systemic nicotine‐induced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental area

TLDR

Stimulation of the mesolimbic dopamine system is key to nicotine’s rewarding and dependence‑producing effects. The study aimed to locate the site of nicotine’s stimulatory action on dopamine release. The authors performed simultaneous microdialysis in the VTA and nucleus accumbens of awake rats, measuring extracellular dopamine and metabolites, and infused the nicotinic antagonist mecamylamine into either region to assess its effect. Systemic nicotine raised dopamine and metabolites by ~50%, an effect blocked by mecamylamine in the VTA but not in the nucleus accumbens; local nicotine infusions increased dopamine similarly in both regions, yet only VTA infusion elevated metabolites, indicating that VTA nicotinic receptors play a greater role in systemic nicotine‑induced dopamine release and that the mesolimbic system is phasically regulated. © 1994 Wiley‑Liss, Inc.

Abstract

Abstract Stimulation of the mesolimbic dopamine (DA) system is considered of major importance for the rewarding and dependence producing properties of nicotine (NIC). To identify the site of this stimulatory action, simultaneous microdialysis was performed in the ventral tegmental area (VTA) and the ipsilateral nucleus accumbens (NAC) of awake rats. Extracellular concentrations of DA and its metabolites were measured in the NAC. NIC (0.5 mg/kg, s.c.) increased DA and its metabolites by ∼50%.Concomitant infusion of the nicotinic receptor antagonist mecamylamine (MEC, 100 μ) through the VTA probe, starting 40 min before NIC injection, antagonized the NIC induced increases of DA and its metabolites. In contrast, similar MEC pretreatment (40 or 140 min) in the NAC did not affect DA or metabolite responses to systemic NIC. Infusion of NIC (1,000 μ) in the NAC or the VTA increased DA release by 49% and 48%, respectively, whereas only the VTA infusion increased metabolite concentrations by ‐25%. MEC infusion (1–1,000 μ) in the VTA did not affect DA or its metabolites, whereas the 1,000 μ 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. Furthermore, our findings support the notion that the mesolimbic dopaminergic system is phasically rather than tonically regulated by nicotinic receptor activation within the VTA. © 1994 Wiley‐Liss, Inc.