The cannabinoid receptor antagonist SR-141716A induces penile erection in male rats: involvement of paraventricular glutamic acid and nitric oxide.
The cannabinoid CB1 receptor antagonist SR141716A (0.5, 1 and 2 microg) 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 NO2- and NO3- in the paraventricular dialysate obtained by means of intracerebral microdialysis. Both penile erection and NO2- increase induced by SR 141716A were reduced by the prior injection into the PVN of the cannabinoid CB1 agonists WIN 55,212-2 (5 microg) or HU 210 (5 microg), given into the paraventricular nucleus at doses unable to induce penile erection or to modify NO2- concentration. SR 141716A responses were also reduced by nitro-L-arginine methylester (20 microg), a non-selective NO synthase inhibitor, S-methyl-L-thiocitrulline (20 microg), a selective neuronal NO synthase inhibitor, the excitatory amino acid NMDA receptor antagonist dizocilpine ((+)MK 801) (1 microg), or the GABAA receptor agonist muscimol (0.2 microg) injected into the PVN 15 min before SR 141716A. In contrast, the inducible NO synthase inhibitor L-N(6)-(1-iminoethyl)lysine (20 microg), the GABAB receptor agonist baclofen (0.2 microg), the mixed dopamine receptor antagonist cis-flupenthixol (10 microg), and the oxytocin receptor antagonist d(CH2)5Tyr(Me)-Orn8 -vasotocin (1 microg), were ineffective. Despite its inability to reduce penile erection and NO2- increase induced by SR 141716A when injected into the PVN, d(CH2)5Tyr(Me)-Orn8 -vasotocin (1 microg) reduced almost completely penile erection without reducing paraventricular NO2- increase when injected into the lateral ventricles 15 min 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.
Melis
Maria Rosaria
MR
Bernard B Brodie Department of Neuroscience and Centre of Excellence for The Neurobiology of Addictions, University of Cagliari, 09042 Monserrato, Italy. mrmelis@unica.it
Succu
Salvatora
S
Mascia
Maria Stefania
MS
Sanna
Fabrizio
F
Melis
Tiziana
T
Castelli
Maria Paola
MP
Argiolas
Antonio
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines; D063387:Cannabinoid Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D010121:Oxytocin / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010410:Penile Erection / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant
D048588:Benzoxazines; D063387:Cannabinoid Receptor Antagonists; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D009569:Nitric Oxide; D018698:Glutamic Acid; D010121:Oxytocin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol; D052248:Nitric Oxide Synthase Type I; C062018:HU 211; D000077285:Rimonabant; D019331:NG-Nitroarginine Methyl Ester