Contributions of Gonadal Hormones in the Sex-specific Organization of Context Fear Learning

It is widely established that gonadal hormones are fundamental to modulating and organizing the sex-specific nature of reproductive behaviors. Recently we proposed that context fear conditioning (CFC) may emerge in a sex-specific manner organized prior to the pubertal surge of gonadal hormones. Here we sought to determine the necessity of male and female gonadal hormones secreted at critical periods of development upon context fear learning. We tested the organizational hypothesis that neonatal and pubertal gonadal hormones play a permanent role in organizing contextual fear learning. We demonstrate that the postnatal absence of gonadal hormones by neonatal orchiectomy (oRX) in males and ovariectomy (oVX) in females resulted in an attenuation of CFC in adult males and an enhancement of CFC in adult females. In females, the gradual introduction of estrogen before conditioning partially rescued this effect. However, the decrease of CFC in adult males was not rescued by introducing testosterone before conditioning. Next, at a further point in development, preventing the pubertal surge of gonadal hormones by prepubertal oRX in males resulted in a reduction in adult CFC. In contrast, in females, prepubertal oVX did not alter adult CFC. However, the adult introduction of estrogen in prepubertal oVX rats reduced adult CFC. Lastly, the adult-specific deletion of gonadal hormones by adult oRX or oVX alone or replacement of testosterone or estrogen did not alter CFC. Consistent with our hypothesis, we provide initial evidence that gonadal hormones at early periods of development exert a vital role in the organization and development of CFC in male and female rats.