Lesions of the mesotelencephalic dopamine system enhance the effects of selective dopamine D₁ and D₂ receptor agonists on striatal acetylcholine release

In vivo microdialysis was uses to determine the effects of 6-hydroxydopamine (6-OHDA) lesions of the mesotelencephalic dopamine system on dopamine receptor agonist induced changes in extracellular acetylcholine (ACh) concentrations in the striatum. Such lesions increased the inhibitory effect of a low dose of the D₂ receptor agonist quinpirole (0.05 mg/kg s.c.) on striatal ACh release. In addition, 6-OHDA lesions enhanced the facilitatory effect of the selective D₁ receptor agonist CY 208-243 on striatal ACh release, enabling a subthreshold (0.2 mg/kg s.c.) dose to increase striatal dialysate concentrations of ACh by over 60%. These results indicate that denervation supersensitivity potentiates both the facilitatory effects of D₁ receptor agonists and the inhibitory effects of D₂ receptor agonists on striatal cholinergic activity. It was also found that the 6-OHDA lesions reduced basal interstitial ACh concentrations by 75% in the ipsilateral striatum. The later results are consistent with the hypothesis that the prepotent action of dopamine in the forebrain is to enhance striatal ACh release via a D₁ receptor mechanism.