Chronic morphine exposure during puberty induces long-lasting changes in opioid-related mRNA expression in the mediobasal hypothalamus
Chronic morphine exposure during puberty induces long-lasting changes in opioid-related mRNA expression in the mediobasal hypothalamus
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DOI：
10.1016/j.brainres.2007.11.018
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发表时间：
2008-01-23
期刊：
影响因子：
2.9
通讯作者：
Byrnes, Elizabeth M.
中科院分区：
文献类型：
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作者：
Byrnes, Elizabeth M.
发育中的女性滥用药物可能对生殖能力产生重大的长期影响。在青春期长期接触吗啡已被证明可以减少泌乳大鼠的泌乳素分泌。中基底下丘脑（MBH）内的阿片活性调节哺乳诱导的催乳素分泌。因此，本研究旨在确定慢性青春期吗啡暴露是否会改变MBH内mu-和/或kappa-阿片受体mRNA或前阿片黑素皮质素（POMC） mRNA的表达。雌性Sprague-Dawley大鼠从30日龄开始，采用递增剂量方案，每天两次注射硫酸吗啡或生理盐水，共20天。几周后，采用定量RT-PCR检测孕母、未怀孕（未产）对照、产后第5天（PPDS）、PPD10、PPD18和孕母、有生育经验（初产）的母鼠MBH内mRNA的表达。青春期吗啡暴露雌鼠在绝经时mu-和kappa受体mRNA表达升高，POMC mRNA表达降低。在哺乳期，同样处理的雌性MBH中mu-和kappa受体mRNA表达减少，而POMC mRNA表达增加。经青春期盐处理的雌性哺乳期间mRNA表达未见变化；然而，与未产对照相比，在初产、青春期经盐处理的雌性中，观察到mu-和kappa受体mRNA表达增加，POMC mRNA表达减少。因此，青春期慢性吗啡暴露导致mu-和kappa受体以及MBH中POMC mRNA表达的长期改变，这与生殖经历后观察到的变化相似。这些变化与泌乳早期泌乳素分泌减少无关；然而，它们确实证明了青春期长期接触阿片类药物对成年期下丘脑阿片类系统的影响的持久性。(c) 2007年Elsevier B.V.出版
Substance abuse in developing females may have significant long-term effects on reproductive competency. Chronic morphine exposure during puberty has been shown to reduce prolactin secretion in lactating rats. Opioid activity within the mediobasal hypothalamus (MBH) regulates suckling-induced prolactin secretion. Thus, the current study was conducted to determine whether chronic pubertal morphine exposure alters the expression of mu- and/or kappa-opioid receptor mRNA or pro-opioimelanocortin (POMC) mRNA within the MBH. Using an increasing dose regimen, female Sprague-Dawley rats were injected twice daily for a total of 20 days with morphine sulfate or saline beginning at 30 days of age. Several weeks later, quantitative RT-PCR was used to determine mRNA expression within the MBH in diestrus, never pregnant (nulliparous) controls, postpartum day 5 (PPDS), PPD10, PPD18, and diestrus, reproductively experienced (primiparous) females. Pubertal morphine exposed females had increased mu- and kappa-receptor mRNA expression as well as decreased POMC mRNA expression on diestrus. During lactation, mu- and kappa-receptor mRNA expression in the MBH decreased while POMC mRNA expression increased in similarly treated females. No changes in mRNA expression were observed during lactation in pubertal saline-treated females; however, increased mu- and kappa-receptor mRNA expression as well as decreased POMC mRNA expression was observed in primiparous, pubertal saline-treated females when compared to nulliparous controls. Thus, chronic morphine exposure during puberty results in long-term alterations in mu- and kappa-receptor as well as POMC mRNA expression in the MBH which are similar to the changes observed following reproductive experience. These changes do not correlate with the decreased prolactin secretion observed during early lactation; however, they do demonstrate the enduring nature of the effects of chronic opiate exposure during puberty on hypothalamic opioid systems in adulthood. (c) 2007 Published by Elsevier B.V.