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The role of perinatal testosterone on exploratory behavior, sexual motivation, and spatial working memory in adult rats

Endocrinology & Metabolism International Journal
Chaya Gopalan,1 Paige Niepoetter,2 Avery Ogle,2 Sai Medavaka,2 Samantha A Olendorff,3 Kevin R Tucker3

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Aim: Sex differentiation occurs during the perinatal period (four days before and after birth) in the rat brain. The brain remains a female brain unless exposed to testosterone, which gets metabolized to 17β-estradiol and dihydrotestosterone. While aromatase converts testosterone to 17β-estradiol, 5α-reductase converts testosterone to dihydrotestosterone. 17β-estradiol exerts its effects by binding to an estrogen receptor, whereas dihydrotestosterone via an androgen receptor. The role of dihydrotestosterone and 17β-estradiol during the organizational phase of brain differentiation was tested using adult rat behaviors. The study sought to examine the effects of perinatal manipulations on adult rat behaviors.
Materials and methods: Timed-pregnant rats received either the vehicle (5% ethanol and 95% sesame oil), exemestane (4 mg/kg/ml; aromatase inhibitor), or flutamide (20 mg/kg/ml; androgen receptor blocker) subcutaneously during the last four days of pregnancy. Pups from each group continued to receive their treatments during the first four days after birth. From postnatal day 65, these animals were subjected to open field, sexual motivation, and spatial working memory tests.
Results: Male rats receiving flutamide exhibited exploratory behavior significantly more compared to exemestane and control groups. Male rats receiving exemestane had substantially higher plasma testosterone and displayed an increased interest in the estrus rat than the control and flutamide group.
Conclusion: Androgen receptor blockade resulted in increased exploratory behavior in male rats where 17β-estradiol was testosterone's primary metabolite. The blocking of aromatase using exemestane resulted in higher levels of plasma testosterone and enhanced sexual motivation in male rats. Thus, 17β-estradiol and dihydrotestosterone's presence during the organizational phase is essential for normal socio-sexual and exploratory behaviors.


Gonadal steroid hormones, Aromatase, Androgen receptors, Sexual dimorphism