Age-related differences in the sensitivity to opiate-induced perturbations in reproductive endocrinology in the developing and adult male rat

The effects of a single morphine pellet (75 mg) implanted in developing male rats at 27 days of age on reproductive endocrine parameters were compared to those found in adult (65-day-old) animals after the same treatment. The pellets were left in place to provide the release of morphine during critical phases of puberty and sexual maturation and to prevent an abrupt withdrawal syndrome upon pellet removal which would confound our results. Developing rats were sacrificed at representative intervals after pellet insertion to assess the development of key indices of reproductive endocrinology; adult rats were sacrificed at the same time intervals to permit an evaluation of age-related differences in the sensitivity to opiate-induced endocrine disturbances. Our results showed that morphine markedly influenced a number of endocrine parameters associated with the maturation of the hypothalamic-pituitary-gonadal axis in developing rats for prolonged periods of time, whereas the effects of the opiate in the adult rat were relatively modest and transient. In the developing rat, serum luteinizing hormone (LH), testosterone, the wet tissue weights of the seminal vesicles and testes and hypothalamic LH-releasing hormone (LHRH) levels were substantially depressed immediately after pellet implantation and these effects persisted for up to 4 weeks when compared to placebo-implanted, age-matched controls. In contrast to these results, adult rats showed only transient effects (<1 week) of morphine on certain reproductive endocrine parameters (e.g. serum LH, testosterone and the weights of the seminal vesicles) and no effects on others (e.g. testes weights and hypothalamic LHRH). Thus, our results demonstrate that exposure to morphine during a critical period in sexual development has much more pronounced effects on reproductive physiology than it does in sexually mature animals. The mechanisms underlying the marked age-related differences in the sensitivity to opiate-induced perturbations in reproductive endocrine parameters are unknown, but several plausible possibilities are discussed.