Oxytocin induces penile erection when injected into the ventral tegmental area of male rats: role of nitric oxide and cyclic GMP.
Oxytocin (80 ng) injected into the caudal mesencephalic ventral tegmental area (VTA) of male rats induces penile erection. Such an effect occurs together with an increase in nitric oxide (NO) production, as measured by the augmented concentration of NO(2)(-) and NO(3)(-) found in the dialysate obtained from this brain area by means of intracerebral microdialysis. Both effects are abolished by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (1 microg), an oxytocin receptor antagonist, by S-methyl-l-thiocitrulline acetate (20 microg), a neuronal NO synthase inhibitor, or by omega-conotoxin GVIA (50 ng), a N-type Ca(2+) channel blocker, all injected into the VTA 15 min before oxytocin. In contrast, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (40 microg), a guanylate cyclase inhibitor, given into the VTA 15 min before oxytocin, abolishes penile erection, but not the increase in NO production, while haemoglobin (40 microg), a NO scavenger, injected immediately before oxytocin reduces the increase in NO production, but not penile erection. 8-Bromo-cyclic guanosine monophosphate (0.5-10 microg) microinjected into the VTA induces penile erection with an inverted U-shaped dose-response curve; the maximal effective dose being 3 microg. Immunohistochemistry reveals that in the caudal VTA oxytocin-containing axons/fibres (originating from the paraventricular nucleus of the hypothalamus) contact cell bodies of mesolimbic dopaminergic (tyrosine hydroxylase-positive) neurons containing both NO synthase and guanylate cyclase. These results suggest that oxytocin injected into the VTA induces penile erection by activating NO synthase in the cell bodies of mesolimbic dopaminergic neurons. NO in turn activates guanylate cyclase present in these neurons, thereby increasing cyclic GMP concentration.
Succu
Salvatora
S
Bernard B Brodie Department of Neuroscience, University of Cagliari, 09042 Monserrato, Italy.
Sanna
Fabrizio
F
Cocco
Cristina
C
Melis
Tiziana
T
Boi
Antonio
A
Ferri
Gian-Luca
GL
Argiolas
Antonio
A
Melis
Maria Rosaria
MR
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D017551:Microdialysis; D009498:Neurotoxins / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism; D020866:omega-Conotoxin GVIA / Q000378:metabolism
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D009498:Neurotoxins; D009566:Nitrates; D009573:Nitrites; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D010121:Oxytocin; D020866:omega-Conotoxin GVIA; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase; D006162:Guanylate Cyclase; D006152:Cyclic GMP