Sexual differentiation of rat reproductive versus opioid antinociceptive systems.

BACKGROUND

It has been suggested that sexual differentiation of opioid analgesic sensitivity may parallel sexual differentiation in reproductive systems.

OBJECTIVE

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.