Abstract

Estradiol sensitization refers to a phenomenon whereby each subsequent injection of estradiol benzoate (EB), when administered to the ovariectomized (OVX) rat to induce sexual behavior, potentiates the occurrence of those behaviors. The goals of the current thesis were to characterize the pattern of estradiol sensitization by varying the EB dose and injection interval, to examine some behavioral, hormonal, and neural factors involved in its induction and maintenance, and to apply it as a diagnostic tool in models that have been shown in the literature to produce sexual inhibition. It was first determined that estradiol sensitization is robustly induced by 10μg EB administered SC every 4 days, and that the effect is further potentiated if EB is administered in the absence of the opportunity to copulate. Furthermore, although adrenal progesterone (P) did not play a role, chronic administration of systemic injections of the P receptor antagonist RU486 revealed that P receptors are important in the maintenance of the sensitization. The next set of experiments determined that vaginocervical stimulation (VCS) received on repeated tests attenuates the sensitization of appetitive sexual behaviors (hops, darts, solicitations), and that inhibitory mechanisms related to estrous termination may be involved, since the attenuation was mimicked by repeated infusions of the glutamate receptor agonist AMPA to the ventrolateral division of the ventromedial hypothalamus in place of copulation. Moreover, the onset of estrous termination was accelerated in estradiol-sensitized animals that were not given the opportunity to copulate. This suggests that estradiol sensitizes mechanisms of sexual excitation and inhibition. The final experimental chapter determined that prenatally androgenized females are not permanently desensitized to the activational effects of EB, since repeated hormone treatments in combination with sexual experience generally restored sexual behaviors and those females also displayed estradiol sensitization. Finally, the inhibitory effect of corncob bedding, as reported recently in the literature, did not prevent estradiol sensitization. In conclusion, the extent of estradiol sensitization, and the duration of behavioral estrus in estradiol-sensitized animals, interacts with sexual experience, particularly VCS. The data presented herein have implications for all research areas investigating the role of estradiol on physiology and behavior.