Inhibitory Effect of Dopamine on Dorsomedial Arcuate Neurons in Rat Brain Slices: Potentiation by Coadministration of Cocaine

Abstract

Whether dopamine (DA) can have a direct effect on the tuberoinfundibular dopaminergic neurons has been a controversial issue. The present report used single-unit recording of neurons in dorsomedial region of the arcuate nucleus, where most tuberoinfundibular dopaminergic neurons are located, to study this question. By focusing our recording in this region, we found that DA in 25–250 nmol ranges inhibited a significant number of arcuate neurons tested (74.2% of 182 units). The inhibitory effect of DA was not only prominent in most cases, it also persisted in low Ca2+, high Mg2+ solution in several trials. Cocaine, a drug of abuse whose main effect is due to its inhibition of DA transporters and increasing the DA concentration in synaptic clefts, also inhibited a significant number of arcuate neurons by itself (51.5% of 97 units), although its effects were lesser than those of DA. Nevertheless, when coadministered with DA, cocaine significantly potentiated the inhibitory effect of DA in 82% of DA-responsive units (n = 39). These results clearly demonstrate that DA exhibits a predominantly inhibitory effect on presumed DA neurons in dorsomedial arcuate nucleus. The effects of cocaine further support this notion.