title: 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 approximately 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 approximately 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 approximately 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. Thus, the D1 and D2 receptors subserve opposing functions on ACh release. The D1/D2 dopaminergic agonist R-apomorphine, at the does of 1 mg/kg, i.p., reduced ACh output by approximately 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.
authors.affiliation: Laboratory of Cholinergic Neuropharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bertorelli
authors.forename: S
authors.initials: S
authors.lastname: Consolo
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D009043:Motor Activity; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D017330:Remoxipride
chemical_list: D001549:Benzamides; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D017330:Remoxipride; D019257:Quinpirole; D001058:Apomorphine; D000109:Acetylcholine