Acute reduction of dopamine levels alters responses of basal ganglia neurons to selective D-1 and D-2 dopamine receptor stimulation

Abstract

Extracellular single unit recording techniques were used to investigate dopamine agonist-induced changes in the tonic activity of globus pallidus neurons in normal control rats, and in rats in which dopamine levels were acutely reduced by α-methyl-para-tyrosine (AMPT) pretreatment. Systemic administration of the nonselective D-1/D-2 agonist apomorphine consistently induced large increases in the firing rates of globus pallidus neurons, as shown previously. The D-1 agonist SKF 38393 frequently induced no change in pallidal cell firing rates with doses up to 20 mg/kg; however, firing rates of 40% of the cells were stimulated by more than 20% of baseline and 14% were partially inhibited after 20 mg/kg SKF 38393. Following AMPT pretreatment, SKF 38393 induced only increases and no changes in activity; no decreases were observed. The D-2 agonist quinpirole typically increased pallidal neuron activity in a dose-dependent manner but was markedly less effective at stimulating pallidal neuron activity than apomorphine. In AMPT-treated rats, quinpirole's effects were significantly attenuated. Consistent with previous results, most cells showed large rate increases when SKF 38393 and quinpirole were coadministered to normal rats; these increases were similar in magnitude to those induced by apomorphine. In contrast to the observation that AMPT treatment altered the responses of globus pallidus neurons to individually administered quinpirole and SKF 38393, neither the increases in pallidal cell activity induced by apomorphine nor those induced by coadministration of SKF 38393 and quinpirole were significantly attenuated in AMPT-treated rats. The results support the idea that stimulation of both D-1 and D-2 receptors appears to be required to induce apomorphine-like changes in basal ganglia output. Moreover, the effects of individually administered D-1 and D-2 agonists observed in normal rats appear to depend upon the degree to which the complementary receptor subtype is stimulated by endogenous dopamine.