The cannabinoid receptor antagonist SR-141716A induces penile erection in male rats: Involvement of paraventricular glutamic acid and nitric oxide
Melis MR, Succu S, Mascia MS, Sanna F,
Melis T, Castelli MP, Argiolas A.
Bernard B Brodie Department of Neuroscience and
Centre of Excellence for The Neurobiology of Addictions,
University of Cagliari, 09042 Monserrato, Italy.
Neuropharmacology. 2006 Feb;50(2):219-28.
ABSTRACTThe cannabinoid CB1 receptor antagonist SR141716A (0.5, 1 and 2mug) induces penile erection when injected into the paraventricular nucleus of male rats. The pro-erectile effect of SR 141716A occurs concomitantly with an increase in the concentration of NO(2)(-) and NO(3)(-) in the paraventricular dialysate obtained by means of intracerebral microdialysis. Both penile erection and NO(2)(-) increase induced by SR 141716A were reduced by the prior injection into the PVN of the cannabinoid CB1 agonists WIN 55,212-2 (5mug) or HU 210 (5mug), given into the paraventricular nucleus at doses unable to induce penile erection or to modify NO(2)(-) concentration. SR 141716A responses were also reduced by nitro-l-arginine methylester (20mug), a non-selective NO synthase inhibitor, S-methyl-l-thiocitrulline (20mug), a selective neuronal NO synthase inhibitor, the excitatory amino acid NMDA receptor antagonist dizocilpine ((+)MK 801) (1mug), or the GABA(A) receptor agonist muscimol (0.2mug) injected into the PVN 15min before SR 141716A. In contrast, the inducible NO synthase inhibitor l-N(6)-(1-iminoethyl)lysine (20mug), the GABA(B) receptor agonist baclofen (0.2mug), the mixed dopamine receptor antagonist cis-flupenthixol (10mug), and the oxytocin receptor antagonist d(CH(2))(5)Tyr(Me)-Orn(8)-vasotocin (1mug), were ineffective. Despite its inability to reduce penile erection and NO(2)(-) increase induced by SR 141716A when injected into the PVN, d(CH(2))(5)Tyr(Me)-Orn(8)-vasotocin (1mug) reduced almost completely penile erection without reducing paraventricular NO(2)(-) increase when injected into the lateral ventricles 15min before SR 141716A. The present results show that SR 141716 induces penile erection by a mechanism (possibly activation of excitatory amino acid neurotransmission), which causes the activation of neuronal NO synthase in paraventricular oxytocinergic neurons mediating penile erection.Anandamide
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