Spontaneous release of acetylcholine in striatum is preferentially regulated by inhibitory dopamine D2 receptors

• Published in: European journal of pharmacology 1996-12, Vol.317 (2-3), p.257-262
• Main Authors: DEBOER, P, HEERINGA, M. J, ABERCROMBIE, E. D
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Chromatography, High Pressure Liquid; Dopamine Agonists - pharmacology; Dose-Response Relationship, Drug; Electrochemistry; Extracellular Space - drug effects; Extracellular Space - metabolism; Fundamental and applied biological sciences. Psychology; Male; Microdialysis; Neostriatum - drug effects; Neostriatum - metabolism; Quinpirole - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(96)00761-3

The dose-related effects of the direct dopamine D2 receptor agonist quinpirole [trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1 H-pyrazolo[3,4-g]quinoline] on the extracellular concentrations of dopamine and acetylcholine in rat striatum were measured using in vivo microdialysis. Quinpirole was administered intraperitoneally at doses of 3, 30, 300, and 3000 micrograms/kg. Acetylcholine measurements were conducted in the presence of 10 nmol/l of the acetylcholinesterase inhibitor neostigmine in the microdialysis perfusate. The 3 micrograms/kg dose of quinpirole elicited a significant 26% decrease in extracellular dopamine level in striatum whereas the extracellular level of acetylcholine was significantly increased by 15%. At the higher doses tested, quinpirole administration produced significant decreases in the extracellular concentrations of both dopamine and acetylcholine. The maximum inhibition of striatal dopamine efflux by quinpirole was 74% and this effect was observed at the 300 micrograms/kg dose. Inhibition of striatal acetylcholine output reached a maximum of 78% after administration of 3000 micrograms/kg quinpirole. ED50 values (microgram/kg) for quinpirole-induced inhibition of release were 12.4 and 240 for striatal dopamine and acetylcholine, respectively. We conclude from these data that dopamine exerts a tonic inhibitory control over spontaneous acetylcholine efflux in striatum that is directly mediated by dopamine D2 receptors.