D1 AND D2 DOPAMINERGIC REGULATION OF ACETYLCHOLINE-RELEASE FROM STRIATA OF FREELY MOVING RATS

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. Copyright © 1990, Wiley Blackwell. All rights reserved