title: 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.
authors.affiliation: Bernard B. Brodie Department of Neuroscience, Center of Excellence for the Neurobiology of Addictions, University of Cagliari, S.P. Sestu-Monserrato, Km 0.700, 09042 Monserrato, Italy. mrmelis@unica.it
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Melis
authors.forename: Salvatora
authors.initials: S
authors.lastname: Succu
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Mascia
authors.forename: Antonio
authors.initials: A
authors.lastname: Argiolas
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal; D001549:Benzamides / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050638:Receptors, Dopamine D4
chemical_list: D001549:Benzamides; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493601:Drd4 protein, rat; D004791:Enzyme Inhibitors; C477501:N-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D010121:Oxytocin; C042951:oxytocin,1-(beta-mercapto-(beta, beta-cyclopentamethylene)propionic acid)-Tyr(OMe)(2)-Orn(8)-; D001058:Apomorphine; D019331:NG-Nitroarginine Methyl Ester