D1 and D2 Dopaminergic Regulation of Acetylcholine Release from Striata of Freely Moving Rats

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Abstract
The effects of selective D1 and D2 dopaminergic agents on the extracellular acetylcholine (ACh) content in striata of freely moving rats were determined by the microdialysis technique. LY 171555, a selective D2 agonist, reduced ACh output by ∼30% within 20 min at the dose of 0.2 mg/kg, i.p., whereas the D2 antagonists (-)-remoxipride (10 mg/kg, s.c.) and L-sulpiride (50 mg/kg, i.p.) induced maximal increases of ∼-50% within 10 and 20 min, respectively. In contrast, the D1 antagonist SCH 23390 (0.25 mg/kg, s.c.) decreased the extracellular ACh content by ∼30% in 20 min, but lower doses-0.025 and 0.05 mg/kg-had no such effect. The stimulation of ACh release by LY 171555 was prevented by (-)-remoxipride but not by SCH 23390(0.25 mg/kg, s.c.) In addition, the D1 agonist SKF 38393 failed to modify the ACh increasing effect of (-)-remoxipride. Thums, the D1 and D2 receptors subserve opposing functions on ACh release. The D1/D2 dopaminergic agonist R-apomorphine, at the dose of I mg/kg, i.p., reduced ACh output by ∼-35% only when D1 receptors were blocked by SCH 23390(0.025 mg/kg, s.c.). The results provide clear in vivo evidence of the tonic inhibition exerted by dopaminergic nigrostriatal input on the cholinergic system of the basal ganglia through D1 and D2 receptors.

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