Potent inhibitory effect of selective D-2 and D-3 agonists on dopamine-responsive dorsomedial arcuate neurons in brain slices of estrogen-primed rats

The possible involvement of dopamine D-2 and D-3 receptors in the action of dopamine (DA) on inhibiting dorsomedial arcuate nucleus (dmARN) neurons in brain slices was determined in this study. Fresh brain slices were prepare d from ovariectomized, estrogen-primed Sprague-Dawley rats and used for ext racellular single-unit recording. The dmARN neurons were first identified b y their inhibitory responses to DA and then tested with PHNO and/or PD12890 7, selective D-1 and D-3 agonists, respectively. PD128907 in 5-50 nmole dos es significantly inhibited the majority of DA-responsive dmARN neurons (86. 3% of 44 units). Moreover, PHNO in 5-25 nmole doses inhibited all DA-respon sive neurons tested (100% of 34 units). The inhibitory effects of PHNO and PD128907 were not only prominent; but also persisted in low Ca2+, high Mg2 medium, indicating that they were acting directly on the recorded neuron. Pretreatment of either raclopride or U99194A, D-2 and D-3 receptor antagoni sts respectively, reversed the effects of DA in a few trials. In contrast, SKF81297, a D-1 receptor agonist, induced variable responses in dmARN neuro ns. These results clearly indicate that DA may act through D-2 and/or D-3 r eceptors to exhibit an inhibitory effect on presumed TIDA neurons in dmARN. (C) 2001 Elsevier Science Inc. All rights reserved.