Spontaneous release of acetylcholine in striatum is preferentially regulated by inhibitory dopamine D-2 receptors

The dose-related effects of the direct dopamine D-2 receptor agonist quinpirole [trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-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 mu g/kg. Acetylcholine measurements were conducted in the presence of 10 nmol/l of the acetylcholinesterase inhibitor neostigmine in the microdialysis perfusate. The 3 mu g/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 mu g/kg dose. Inhibition of striatal acetylcholine output reached a maximum of 78% after administration of 3000 mu g/kg quinpirole. ED(50) values (mu g/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 D-2 receptors.