Reproductive Consequences of Pubertal Morphine Abuse

描述（由申请人提供）：本提案将研究 青春期滥用鸦片对未来生殖健康的影响。在两个老鼠 青春期是人类的生殖周期， 荷尔蒙节律开始出现。因为内源性阿片类物质介导了一些 这些变化，在此期间人为升高阿片类药物的水平， 干扰生殖发育。虽然一些急性影响的 青春期女性使用的吗啡、海洛因和美沙酮等阿片类药物， 描绘，阿片类药物滥用的长期影响，在动荡的 青春期是未知的。最近的初步研究表明， 在青春期左右对雌性大鼠施用吗啡会导致 在停药后数周可以观察到生殖改变。 具体来说，当这些雌性生下健康的幼崽时， 其后代的生长速度会减慢。此外， 在哺乳引起的催乳素释放中的作用。鉴于正相关性 催乳素分泌和产奶量之间的关系，催乳素分泌减少 可能导致幼犬生长减缓使用慢性递增剂量方案， 吗啡（从30至50日龄每天注射两次），目前的一套 的研究将检查可能的神经内分泌改变， 既有利于减少[在]吸吮诱导催乳素分泌， 幼犬生长速度减慢。其中包括检查催乳素水平 垂体前叶的含量和信息，μ-阿片的敏感性 和D2多巴胺受体亚型调节催乳素分泌， 催乳素受体在乳腺中的表达。此外该 哺乳诱导的催乳素分泌改变的寿命和减少 将检查幼仔的生长情况。本提案的长期目标是利用 这些研究是作为青春期女性药物成瘾的动物模型。给定 最近滥用海洛因的少女人数增加，这些研究 将提供一些潜在的生殖后果的信息， 这可能会出现在未来的女孩上瘾鸦片在这期间， 敏感发育期。

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.