Suppression of cholinergic activity via the dopamine D2 receptor in the rat striatum

The effect of dopamine (DA) D2 receptor on extracellular choline (Ch) and acetylcholine (ACh) levels in rat caudate-putamen (striatum) was investigated by means of microdialysis. The systemic, intraperitoneal (i.p.), injection of (+/-)-2-(N-phenylethyl-N-propyl) amino-5-hydroxytetralin (N-434), a specific DA D2 receptor agonist decreased striatal ACh release in a dose-dependent manner and the i.p. injection of sulpiride, a specific DA D2 receptor antagonist, increased the ACh release in a dose-dependent manner. In contrast, extracellular Ch levels were increased by the agonist and decreased by the antagonist. An increased Ch uptake was observed in sulpiride-treated rats and a decreased Ch uptake was observed in N-434-treated rats. The effects of the D2 agonist on extracellular Ch, ACh and Ch uptake were completely antagonized by the D2 antagonist. These results suggest clearly an inhibition of ACh release by D2 receptor activation, contrasting with previous findings on DA-ACh interaction. The inverse relationship between extracellular Ch and ACh reflects a change in the Ch uptake owing to a change in cholinergic neuron activity via the D2 receptor mechanisms.