A selective oxytocin antagonist attenuates progesterone facilitation of female sexual behavior.
Although previous studies have demonstrated that exogenous administration of oxytocin (OT) enhances sexual receptivity in female rats, there is no compelling evidence that endogenous OT has a physiological role in the regulation of female sexual behavior. In the current studies we centrally administered d(CH2)5[Tyr(Me)2Thr4,Tyr-NH2(9)]ornithine vasotocin (or OTA), a selective OT receptor antagonist, to block endogenous OT in ovariectomized females primed with different levels of gonadal steroids. After OTA administration (100-1000 ng), females primed with estradiol benzoate (EB; 1 microgram) and progesterone (P; 250 micrograms) showed reductions in both receptive and proceptive behaviors. These effects of OTA were also evident, though less striking, in females primed with higher doses of EB (10 micrograms) and P (250 micrograms), but significant OTA effects were absent in females primed with EB (10 micrograms) alone. Thus, OTA appeared to attenuate P's facilitation of sexual behavior. Surprisingly, these behavioral effects of OTA administration were not apparent immediately, but emerged only when OTA was given with P 4-6 h before behavioral testing. To determine if these delayed, but lasting, behavioral effects were associated with OTA occupancy of the OT receptor, we measured OT receptor binding ex vivo using receptor autoradiography. Six hours after intracerebroventricular administration of OTA (1000 ng), OT receptor binding was reduced at least 75% in the ventromedial nucleus of the hypothalamus relative to control levels of binding. Thus, those OT receptors previously implicated in the regulation of sexual receptivity appear to be significantly blocked throughout the period of OTA's behavioral effects. Together, these studies lend support to the hypothesis that endogenous OT has a physiological role in the regulation of female sexual behavior.
Witt
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DM
Laboratory of Clinical Science, National Institute of Mental Health, Poolesville, Maryland 20837.
Insel
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TR
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008141:Lordosis; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D018045:Receptors, Oxytocin; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D014828:Vocalization, Animal / Q000187:drug effects
C055830:KB 5-21; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D011374:Progesterone; D004958:Estradiol; D010121:Oxytocin