Local perfusion of nicotine differentially modulates somatodendritic dopamine release in the rat ventral tegmental area after nicotine preexposure.

We examined the effects of nicotine perfusion into the ventral tegmental area (VTA) on extracellular dopamine (DA) levels in rats using in vivo microdialysis. Local perfusion with nicotine for 80 min (10-100 microM) modestly increased (approximately 105-131% of basal) the extracellular DA levels in the VTA of rats that had been pretreated with saline for 5 days. In animals that had been pretreated with nicotine for 5 days (0.3 mg/kg, s.c.), perfusion with nicotine for 80 min (10-100 microM) dose-dependently increased the extracellular DA levels in the VTA of rats and did so to a greater extent than in saline-pretreated animals (125-171% of basal). Co-perfusion through the dialysis probe with 100 microM mecamylamine, a nonselective nicotinic acetylcholine receptor (nAChR) antagonist, or 100 microM dihydro-beta-erythroidine, a high affinity and competitive nAChR antagonist, attenuated the enhancement of extracellular DA levels produced by 100 microM nicotine alone. These results suggest that local nicotine challenge potentiated the somatodendritic DA release after nicotine preexposure by stimulation of high-affinity nAChRs in the VTA.