The mesolimbic system participates in the naltrexone-induced reversal of sexual exhaustion: opposite effects of intra-VTA naltrexone administration on copulation of sexually experienced and sexually exhausted male rats.
Male rats allowed to copulate until reaching sexual exhaustion exhibit a long-lasting sexual behavior inhibition (around 72 h) that can be reversed by systemic opioid receptor antagonist administration. Copulation activates the mesolimbic dopaminergic system (MLS) and promotes endogenous opioid release. In addition, endogenous opioids, acting at the ventral tegmental area (VTA), modulate the activity of the MLS. We hypothesized that endogenous opioids participate in the sexual exhaustion phenomenon by interacting with VTA opioid receptors and consequently, its reversal by opioid antagonists could be exerted at those receptors. In this study we determined the effects of intra-VTA infusion of different doses of the non-specific opioid receptor antagonist naltrexone (0.1-1.0 μg/rat) on the already established sexual behavior inhibition of sexually exhausted male rats. To elucidate the possible involvement of VTA δ-opioid receptors in the naltrexone-mediated reversal of sexual exhaustion, the effects of different doses of the selective δ-opioid receptor antagonist, naltrindole (0.03-1.0 μg/rat) were also tested. Results showed that intra-VTA injection of 0.3 μg naltrexone reversed the sexual inhibition of sexually exhausted rats, evidenced by an increased percentage of animals capable of showing two successive ejaculations. Intra-VTA infused naltrindole did not reverse sexual exhaustion at any dose. It is concluded that the MLS is involved in the reversal of sexual exhaustion induced by systemic naltrexone, and that μ-, but not δ-opioid receptors participate in this effect. Intra-VTA naltrexone infusion to sexually experienced male rats had an inhibitory effect on sexual activity. The opposite effects of intra-VTA naltrexone on male rat sexual behavior expression of sexually experienced and sexually exhausted rats is discussed.
Departamento de Farmacobiología, Cinvestav Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, Delegación Tlalpan, C.P. 14330, México D.F., Mexico; Departamento de Neuromorfología Funcional, Dirección de Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Av. México-Xochimilco 101, Col. San Lorenzo Huipulco, C.P. 14370, México, D.F., Mexico.
René
R
Garduño-Gutiérrez
Martha
M
León-Olea
Gabriela
G
Rodríguez-Manzo
D000818:Animals; D003307:Copulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D012527:Satiation / Q000187:drug effects* / Q000502:physiology; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C055382:naltrindole
Endogenous opioid; Mesolimbic system; Mu/delta opioid receptor; Sexual exhaustion; Sexually experienced rat; Ventral tegmental area naltrexone