Dopamine D₁ receptor stimulation increases striatal acetylcholine release in the rat

The effect of selective D₁ receptor agonists on acetylcholine (ACh) release in the striatum was investigated using in vivo microdialysis. Administration of the reactive enantiomer, (+)-SKF 38393 (2, 10 mg/kg s.c.), doses which elevate grooming and sniffing behaviour, increased ACh release by 40 and 75%, respectively. Another D₁ receptor agonist CY 204-283 (1 mg/kg s.c.) also produced a 75% increase in ACh output. The racemate (±)-SKF 38393 (20 mg/kg s.c.) increased ACh output by 60% and this was completely blocked by the D₁ receptor antagonist SCH 23390 (0.3 mg/kg s.c.). In contrast, administration of the D₂ receptor antagonist raclopride (1 mg/kg s.c.), 60 min after (±)-SKF 38393 (20 mg/kg s.c.), further increased ACh release. These results suggest that activation of D₁ receptors increases ACh release in vivo and that D₁ and D₂ receptors have opposing roles in the regulation of striatal ACh release.