Activation of dopamine D1 receptors does not affect D2 receptor-mediated inhibition of acetylcholine release in rabbit striatum

Summary The possible involvement of dopamine D₁ receptors in the regulation of acetylcholine release in the rabbit caudate nucleus was investigated. Caudate slices, preincubated with [³H]choline, were superfused continuously and subjected to electrical field stimulation with only a single pulse. In agreement with the view that the release of acetylcholine evoked by a single electrical pulse is not influenced by endogenous transmitters, atropine and domperidone failed to icnrease the evoked release of [³H]acetylcholine, whereas oxotremorine and quinpirole caused a concentration-dependent inhibition of transmitter release. Neither the dopamine D₁ receptor antagonist SCH 23390 nor the Dt agonist SKF 38393 in a concentration range of 0.01–1 mol/l changed the evoked [³H]acetylcholine release. The inhibitory effect of the dopamine D₂ receptor agonist quinpirole was virtually abolished in the presence of 0.1 mol/l domperidone and diminished in the presence of 1 mol/l SCH 23390. It remained unchanged in the presence of 1 mol/l SKF 38393. It is concluded that the inhibition of acetylcholine release by dopamine is mediated exclusively via presynaptic dopamine D₂ receptors and that the antagonistic effect of SCH 23390 on the inhibition of acetylcholine release by quinpirole is due to its interaction with dopamine D₂ rather than D₁ receptors located on cholinergic nerve terminals.Send offprint requests to C. Allgaier at the above address