PD-168077, a selective dopamine D 4 receptor agonist, induces penile erection when injected into the paraventricular nucleus of male rats

Abstract

The effect of PD-168077 ( N-methyl-4-(2-cyanophenyl)piperazynil-3-methylbenzamide maleate), a selective D 4 dopamine receptor agonist, injected into the paraventricular nucleus of the hypothalamus on penile erection was studied in male rats. PD-168077 (1–200 ng) induced penile erection in a dose-dependent manner. The minimal effective dose was 50 ng, while the maximal response was found with 200 ng of the compound, which increased penile erection episodes from 0.3 ± 0.03 to 1.7 ± 0.21. The proerectile effect of PD-168077 was reduced almost completely by L-745,870 (3-(4-[chlorophenyl]piperazin-1-yl)-methyl-1 H-pyrrolo[2,3- B]pyridine trihydrochloride), a selective D 4 dopamine receptor antagonist, (1 μg) given into the paraventricular nucleus before the D 4 dopamine agonist, and by other nonselective dopamine receptor antagonists, such as haloperidol (1 μg) and clozapine (1 μg), which block all dopamine receptor subtypes. The pro-erectile effect of PD-168077 was also reduced by the NO synthase inhibitor N G -nitro- l-arginine methylester (25 μg), but not by the oxytocin receptor antagonist d(CH 2) 5Tyr(Me) 2-Orn 8-vasotocin (1 μg), when given into the paraventricular nucleus. In spite of its inability to prevent the pro-erectile effect of PD-168077 when given in the paraventricular nucleus, d(CH 2) 5Tyr(Me) 2-Orn 8-vasotocin (1 μg) reduced almost completely PD-168077-induced penile erection when given into the lateral ventricles. The present results show that D 4 dopamine receptors present in the paraventricular nucleus may influence penile erection by modulating the activity of paraventricular oxytocinergic neurons mediating erectile function.