Effects of Perinatal Inhibition of Gonadal Steroid Hormones on Behavioral Changes in Rats

Abstract

Sex differentiation of a rat brain occurs during the perinatal period (four days prior to and four days after birth). The undifferentiated brain becomes a female brain unless it is exposed to testosterone (T) which gets metabolized to 17β‐estradiol (E2) and dihydrotestosterone (DHT). While aromatase converts T to E2, 5α‐reductase converts T to DHT. 17β‐estradiol exerts its effects by binding to an estrogen receptor (ER) whereas DHT via an androgen receptor (AR). We tested the significance of DHT and E2 during the organizational phase in the differentiation of the rat brain. During the last four days of pregnancy, seven timed‐pregnant rats received either the vehicle (5% ethanol and 95% sesame oil), exemestane (Aromasin; 4mg/kg/ml), or flutamide (20 mg/kg/ml) subcutaneously. Pups from each group continued to receive their specific treatments during the first four days after birth. From postnatal day 65, these animals were subjected to open field (OF), spatial working memory, and sexual motivation (SM) tests. Male rats receiving flutamide exhibited a significant increase in exploratory behavior. Additionally, male rats receiving exemestane exhibited significantly greater interest in the estrus rat compared to the control group. In conclusion, under AR blockade, where E2 becomes the main gonadal hormone, improvements in exploratory behavior in male rats were observed. Moreover, when exemestane was used to block E2 conversion, and DHT becomes the main gonadal hormone, increased SM in male rats was observed. Thus, the presence of both E2 and DHT during organizational phase appears to be essential for normal socio‐sexual and exploratory behaviors.