PD-168077, a selective dopamine D4 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 D4 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-1H-pyrrolo[2,3-B]pyridine trihydrochloride), a selective D4 dopamine receptor antagonist, (1 microg) given into the paraventricular nucleus before the D4 dopamine agonist, and by other nonselective dopamine receptor antagonists, such as haloperidol (1 microg) and clozapine (1 microg), which block all dopamine receptor subtypes. The pro-erectile effect of PD-168077 was also reduced by the NO synthase inhibitor NG-nitro-L-arginine methylester (25 microg), but not by the oxytocin receptor antagonist d(CH2)5Tyr(Me)2-Orn8-vasotocin (1 microg), 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(CH2)5Tyr(Me)2-Orn8-vasotocin (1 microg) reduced almost completely PD-168077-induced penile erection when given into the lateral ventricles. The present results show that D4 dopamine receptors present in the paraventricular nucleus may influence penile erection by modulating the activity of paraventricular oxytocinergic neurons mediating erectile function.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Melis MR,Succu S,Mascia MS,Argiolas A

doi

10.1016/j.neulet.2004.12.053

keywords:

subject

Has Abstract

pub_date

2005-04-29 00:00:00

pages

59-62

issue

1

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(04)01590-3

journal_volume

379

pub_type

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