Spontaneous release of acetylcholine in striatum is preferentially regulated by inhibitory dopamine D2 receptors.
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.
DeBoer
P
P
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, USA.
Heeringa
M J
MJ
Abercrombie
E D
ED
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D000109:Acetylcholine