Dopamine Depletion Preferentially Impairs D1 over D2‐Receptor Regulation of Striatal In Vivo Acetylcholine Release

Abstract

The roles of D₂ and D₁ dopaminergic receptors on the regulation of striatal acetylcholine (ACh) release in vivo were examined for a period of 120 min after acute (2 h) or prolonged (16 h) depletion of brain dopamine (DA) by a-methyl-p-tyrosine. The reduction of DA transmission did not affect basal ACh output after 2 h but markedly lowered ACh release by 16 h (50%). Acute α-methyl-p-tyrosine pre-treatment prevented the reduction of ACh release by the D, antagonist SCH 23390 and its increase by the D₂ antagonist, remoxipride, consistent with a drastic reduction of DA transmission at both DA receptors. However, 16 h after α-methyl-p-tyrosine, the effect of remoxipride on ACh release was restored, but SCH 23390 still had no effect, suggesting that the D₂ inhibitory tone on ACh release had recovered, whereas the reduction of the D₁ facilitatory influence persisted. The D₁ facilitatory control of ACh neurotransmis-sion thus appears to be more sensitive than the D₂ inhibitory control to a reduction in DA transmission. The new model of DA-ACh interaction resulting from these data casts fresh light on the relationship between changes in DA transmission and extrapyramidal motor function.