Reproductive Consequences of Pubertal Morphine Abuse

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DESCRIPTION (provided by applicant): The present proposal will study the impact of opiate abuse during puberty on future reproductive health. In both the rat and human, puberty is a period during which the reproductive cycles and daily hormonal rhythms begin to emerge. Because endogenous opioids mediate some of these changes, artificially elevated levels of opioids during this period can interfere with reproductive development. While some of the acute effects of opiates like morphine, heroin, and methadone in pubertal females have been delineated, the long-term effects of opiate abuse during the tumultuous pubertal period are unknown. Recent preliminary studies indicate that administering morphine to female rats around the time of puberty results in reproductive alterations that can be observed weeks after drug withdrawal. Specifically, while these females give birth to healthy pups, the rate of growth of their offspring is reduced. Moreover, there appears to be a decrease in the suckling-induced release of prolactin. Given the positive correlation between prolactin secretion and milk yield, a reduction in prolactin secretion could underlie reduced pup growth. Using a chronic increasing dose regimen of morphine (twice daily injections from age 30 to 50 days old), the present set of studies will examine the possible neuroendocrine alterations that may subserve both the decrease [in] suckling-induced prolactin secretion and decreased pup growth. These include examination of the level of prolactin content and message in the anterior pituitary, the sensitivity of the mu-opioid and D2 dopamine receptor subtypes to modulate prolactin secretion, and the expression of prolactin receptors in the mammary gland. In addition, the longevity of alterations in suckling-induced prolactin secretion and reduced pup growth will be examined. The long-term objective of this proposal is to use these studies as an animal model of drug addiction in adolescent females. Given the recent rise in the number of adolescent girls abusing heroin, these studies will provide information on some of the potential reproductive consequences that may arise in the future for girls addicted to opiates during this sensitive developmental period.