Is in vivo striatal acetylcholine output under a tonic inhibitory control by dopamine?

The role of dopamine transmission on striatal acetylcholine release was investigated by using brain microdialysis. Blockade of dopamine D-2 receptors with (-)-sulpiride or haloperidol increased acetylcholine release to a maximum of 80% (after 50 and 0.5 mg/kg, respectively). This effect was prevented by blockade of dopamine D-1 receptors with 0.5 mg/kg SCH 39166 or by depletion of dopamine stores after 5 mg/kg reserpine + 150 mg/kg alpha-methyltyrosine. Treatment with SCH 39166 or reserpine + alpha-methyltyrosine reduced acetylcholine release by about a maximum of 30%. Stimulation of dopamine D-2 receptors with LY 171555 (quinpirole) at a low, sedative dose (0.05 mg/kg), reduced acetylcholine release by about 30% with no further reduction at higher doses up to 1 mg/kg. Moreover, LY 171555 (0.1 mg/kg) given to SCH 39166 (0.5 mg/kg) or SKF 38393 (20 mg/kg)-pretreated rats did not decrease acetylcholine release, suggesting that its effect is through a dopamine D-1 receptor-mediated mechanism. In contrast, in dopamine depleted rats, LY 171555 0.1 mg/kg became more effective in decreasing acetylcholine release (about 70%) also after SCH 39166 (0.5 mg/kg) pretreatment (about 80%), thus acting independently of dopamine D-1 receptor mechanisms. These results indicate that, in normal circumstances, endogenous dopamine facilitates striatal acetylcholine release through dopamine D-1 receptors. The results argue against the commonly accepted view that dopamine D-2 receptors exert a tonic inhibitory control on acetylcholine release. Moreover, they suggest that dopamine D-2 receptors, in circumstances of dopamine depletion, may exert an inhibitory control on acetylcholine release independent of dopamine D-1 receptor mechanisms.