We investigated whether D-1 dopaminergic receptors modulate in vivo acetylcholine output in the shell and core areas of rat nucleus accumbens using the microdialysis technique. Subcutaneous injection (1, 2 and 3 mg/kg) of the D-1 agonist SKF 82958 enhanced acetylcholine output in both areas of the nucleus accumbens while the selective D-1 antagonist SCH 39166 (0.15 and 0.30 mg/kg, s.c.) lowered it. Both SKF 82958 and SCH 39166 were more effective in the shell than in the core region. The increase in acetylcholine release induced by SKF 82958 in the shell was tetrodotoxin-sensitive. The dopamine release inducer d-amphetamine (1 and 2 mg/kg, s.c.) and the dopamine uptake inhibitor cocaine (IO and 20 mg/kg, i.p.) dose-dependently raised acetylcholine release in the shell and core areas. The dopaminergic stimulants, like the direct-acting D-1 compounds, were more effective in the shell than in the core compartment of the nucleus accumbens. The acetylcholine increases in the shell induced by d-amphetamine (2 mg/kg), cocaine (20 mg/kg) and SKF 82958 (3 mg/kg) were antagonized by the D-1 antagonists SCH 39166 (5 mu M) and SCH 23390 (10 mu M), applied locally by reverse dialysis. The results suggest that dopamine acting at the D-1 receptors exerts a tonic stimulatory control over the cholinergic function of the shell and core compartments of the nucleus accumbens with the shell being more strongly influenced. (C) 1999 IBRO. Published by Elsevier Science Ltd.