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阿片类药物对未来生殖健康的影响。在两只大鼠中 和人类一样，青春期是一个生殖周期和日常 荷尔蒙节律开始出现。因为内源性阿片类药物介导了一些 这些变化，在此期间人为地提高了阿片类药物的水平 干扰生殖发育。虽然一些严重的影响， 青春期女性中的阿片类药物，如吗啡、海洛因和美沙酮 描述，阿片类药物滥用在骚乱期间的长期影响 青春期是未知的。最近的初步研究表明， 雌性大鼠在青春期前后注射吗啡会导致 停药几周后可观察到的生殖改变。 具体地说，当这些雌性产下健康的幼崽时， 它们后代的生长速度会减慢。此外，这一数字似乎有所下降。 在哺乳诱导的催乳素释放过程中。鉴于这种正相关关系 在催乳素分泌和产奶量之间，催乳素分泌减少 可能是幼崽生长减慢的原因。使用慢性递增剂量方案 吗啡(从30日龄到50日龄每天注射两次)，本套 的研究将检查可能的神经内分泌变化，可能 抑制哺乳诱导的催乳素分泌的减少和 幼崽生长速度减慢。这些检查包括检查催乳素水平 Mu阿片类药物在垂体前叶的含量和信息敏感性 和D2多巴胺受体亚型来调节催乳素的分泌，以及 催乳素受体在乳腺中的表达此外， 哺乳诱导的催乳素分泌和减少的改变的寿命 我们将检查幼崽的生长情况。这项提议的长期目标是使用 这些研究作为青春期女性吸毒成瘾的动物模型。vt.给出 这些研究表明，最近滥用海洛因的青春期女孩数量有所上升 将提供有关一些潜在的生殖后果的信息 在此期间，对鸦片类药物上瘾的女孩未来可能会出现这种情况 发育敏感期。

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.