OPPOSING ROLES FOR DOPAMINE D-1 AND D-2 RECEPTORS IN THE REGULATION OF HYPOTHALAMIC TUBEROINFUNDIBULAR DOPAMINE NEURONS

The purpose of the present study was to characterize pharmacologically dopamine D-1 receptor-mediated inhibition of tuberoinfundibular dopam ine neurons in males rats, and to determine if inhibitory dopamine D-1 receptors oppose stimulatory dopamine D-2 receptors and account for t he inability of mixed dopamine receptor agonists to alter the activity of these neurons. Tuberoinfundibular dopamine neuronal activity was e stimated by measuring the concentrations of the dopamine metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) in the median eminence, the regio n of the hypothalamus containing terminals of these neurons. Administr ation of the dopamine D-1 receptor agonist(+/-)-1 nyl-2,3,4,5-tetrahyd ro-(1H)-3-benzazepine-7,8-diol (SKF38393) decreased median eminence DO PAC and increased plasma prolactin concentrations, whereas administrat ion of the dopamine D-1 receptor antagonist 7a,8,9,13b-hexahydro-3-chl oro-2-hydroxy-N-methyl-5 H-benzo[d]naphtho-[2,1b]azepine (SCH39166) in creased median eminence DOPAC concentrations but had not effect on pla sma prolactin. The inhibitory effect of SKF38393 on median eminence DO PAC concentrations was blocked by SCH39166. These results demonstrate that acute activation of dopamine D-1 receptors inhibits the activity of tuberoinfundibular dopamine neurons and thereby increases prolactin secretion, and that under basal conditions dopamine D-1 receptor-medi ated inhibition of tuberoinfundibular dopamine neurons is tonically ac tive. Administration of the dopamine D-2 receptor agonist ctahydro-6-p ropyl-pyridol[2,3-g]quinazolin-2-amine (quinelorane) increased median eminence DOPAC concentra tions, and SKF38393 caused a dose-dependent r eversal of this effect. Administration of the mixed dopamine D-1/D-2 r eceptor agonist R(-)-10,11-dihydroxy-apomorphine (apomorphine) had no effect per se, but blocked quinelorane-induced increases in DOPAC conc entrations in the median eminence. These results reveal that concurren t activation of dopamine D-1 and D-2 receptors nullifies the actions o f each of these receptors on tuberoinfundibular dopamine neurons, whic h likely accounts for the lack of an acute effect of mixed dopamine D- 1/D-2 receptor agonists on these hypothalamic dopamine neurons. (C) 19 98 Elsevier Science B.V. All rights reserved.