Regulation of dopamine D1 and D2 receptors on striatal acetylcholine release in rats

The effects of dopamine (DA) D1 and D2 receptors on striatal acetylcholine (ACh) releases were investigated by in vivo microdialysis. All drugs were applied via dialysis membrane directly to the striatum. The levels of ACh release were increased by 10(-4) M SKF38393, a D1 receptor agonist. Although 10(-4) M SCH23390, a D1 receptor antagonist, exhibited an increase in the levels of ACh release, the agonist (10(-4) M) induced-increase in the levels of ACh release was suppressed by coperfusion of the antagonist (10(-4) M). In contrast, the levels of ACh release were decreased by the D2 receptor agonist, N-434, in a dose-dependent manner (10(-4) M to 10(-7) M) and increased by the D2 receptor antagonist, sulpiride, in a dose-dependent manner (10(-5) M to 10(-7) M). The agonist (10(-5) M) induced-decrease in the levels of ACh release was suppressed by coperfusion of the antagonist (10(-4) M). Coperfusion of D1 (10(-4) M) and D2 (10(-5) M) agonists blocked both effects of respective drug alone. In order to clarify the effect of endogenous DA, two drugs with different mechanisms for enhancing DA concentration in the synaptic cleft, the DA release-inducer methamphetamine, and the DA uptake inhibitor nomifensine were perfused separately. Both (10(-4) M to 10(-5) M) produced a dose- and a time-dependent decrease in the levels of ACh release. Significant higher levels of ACh release were observed in the striatum of the 6-hydroxydopamine (8 micrograms/10 microliters)-treated rats with significant depletion of striatal DA content. These results suggest that in striatal DA-ACh interaction ACh release, as cholinergic interneuron's activity, is tonically inhibited via the D2 receptor, mainly by dopaminergic input, and the D1 receptor probably modifies the effect of the D2 receptor indirectly.