Differential regulation of release of acetylcholine in the striatum in mice following continuous exposure to selective D₁ and D₂ dopaminergic agonists

The effect of continuously infusing the selective D₁ and D₂ dopamine receptor agonists, SKF 38393 and quinpirole, on the release of [³H]acetylcholine from prelabeled striatal slices was investigated. These biochemical parameters were correlated with the behavioral effects of these agonists. Acute injections of SKF 38393 or quinpirole did not affect either K⁺-stimulated or spontaneous release of [³H]acetylcholine. Chronic exposure to quinpirole reduced the K⁺-evoked release of [³H]acetylcholine by 25.7%; long-term treatment with SKF 38393 did not alter the release of [³H]acetylcholine, induced by K⁺ stimulation. Added in vitro, SKF 38393 increased the release of [³H]acetylcholine, from striatal slices. The effect of the D₁ dopamine receptor agonist,, SKT 38393 was reduced after 7-days of infusion of SKF 38393 but was enhanced by 7-days of infusion of quinpirole. Activation of D₂ dopamine receptors with quinpirole or of muscarinic receptors with carbachol induced an inhibition of release of [³H]acetylcholine. Chronic treatment with quinpirole diminished the response to the in vitro addition of quinpirole. The ability of carbachol to inhibit release of acetylcholine was not altered by continuous treatment with either SKF 38393 or quinpirole. Continuous infusion of SKF 38393 produced an initial grooming behavior; this behavior disappeared by 2 hr and remained absent during the 7 days of infusion of SKF 38393. Similarly, continuous administration of quinpirole produced stereotyped behavior, which peaked at 1 hr and disappeared by 4 hr and remained absent for the duration of the infusion. These findings demonstrate that continuous exposure to D₁ or D₂ agonists caused receptor-selective functional desensitization of D₁ or D₂ dopamine receptors. The results also indicate that the D₁ and D₂ dopamine receptor systems, involved in the regulation of release of acetylcholine, may be functionally interrelated.