The present study compared organizational and activational roles of
testosterone in sexual differentiation in reproductive versus
opioid antinociceptive systems in the rat, to assess whether both systems were similarly
testosterone dependent.
METHODS: Male rat pups (Sprague-Dawley and Fisher 344 [F344]) were either handled or castrated on postnatal day (PND) 1, and female pups were injected with
testosterone propionate (100 or 1000 microg) on PND 2. In adulthood, all rats were gonadectomized (or simply anesthetized) and implanted with either
testosterone filled or blank capsules (one 10-mm
capsule/100 g of
body weight).
RESULTS: Two hundred one Sprague-Dawley rats and 178 F344 rats were used. In gonadally intact adults of both rat strains, the antinociceptive potency of subcutaneously injected
morphine was significantly greater in males than in females (P < or = 0.05). These sex differences were eliminated by neonatal
castration in males or by neonatal
androgenization in females. However, adult
testosterone treatment reversed the effects of neonatal
castration in males. Masculinization and defeminization of sexual behavior, ovary weight, and
body weight generally met conventional expectations. Compared with male controls, neonatally castrated males gained less
body weight, and displayed more
lordosis behavior and compromised male sexual behaviors. Compared with female controls, neonatally androgenized females gained more
body weight, developed smaller ovaries, and presented less
lordosis behavior and more male sexual behaviors. Overall, neonatal
testosterone manipulations sufficient to masculinize or defeminize rats in terms of reproductive behavior and physiology also masculinized or defeminized
morphine antinociceptive sensitivity. The effects of neonatal
castration were reversed by adult
testosterone treatment, indicating that sexual differentiation of
opioid antinociceptive systems begins before PND 1.
CONCLUSIONS: Sensitivity to
opioid antinociception begins to diverge between males and females early in life. The relationship between
gonadal hormone-mediated sexual differentiation of the reproductive and the
opioid antinociceptive systems suggests that the 2 systems may be functionally linked. This finding has implications for the treatment of
pain and
analgesia in women and men.