The effect of cannabinoid CB1 receptor agonists and antagonists on penile erection was studied in male rats when injected into the paraventricular nucleus of the hypothalamus. The CB1 receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide) (0.5–5 μg) induced penile erection in a dose-dependent manner. The minimal effective dose was 1 μg, while the maximal response was found with 5 μg of the compound. In contrast, the CB1 receptor agonists WIN 55,212-2 (4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo(3,2,1-I,j)quinolin-6-one) (0.5–5 μg) and CP 55,940 (1α,2β-(R)-5α)-5-(1,1-dimethylheptyl)-2-(5-hydroxy-2-(3-hydroxy-propyl)cyclohexyl)phenol (0.5–5 μg) were ineffective at all the doses tested. Nevertheless, both compounds reduced the enhancing effect of SR 141716A on penile erection when given into the paraventricular nucleus at the above doses before SR 141716A. The pro-erectile effect of SR 141716A was also reduced by the non-competitive NMDA receptor antagonist dizolcipine (MK-801) (0.2 μg) and by the NO synthase inhibitor NG-nitro- l -arginine methylester (L-NAME) (20 μg) but not by the dopamine receptor antagonist cis-flupenthixol (10 μg) or the oxytocin receptor antagonist d(CH 2 ) 5 Tyr(Me) 2 -Orn 8 -vasotocin (0.1 μg), when given into the paraventricular nucleus. In spite of its inability to prevent the pro-erectile effect of SR 141716A when given in the paraventricular nucleus, d(CH 2 ) 5 Tyr(Me) 2 -Orn 8 -vasotocin) (1 μg) reduced almost completely SR 141716A-induced penile erection when given into the lateral ventricles. The present results show that cannabinoid CB1 receptors present in the paraventricular nucleus may influence erectile function and sexual activity by modulating paraventricular oxytocinergic neurons mediating erectile function.
Neuroscience Letters – Elsevier
Published: Apr 8, 2004
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