Molnar J, He J R, Barraclough C A
Department of Physiology, School of Medicine, University of Maryland, Baltimore 21201-1559.
Brain Res Mol Brain Res. 1994 Mar;22(1-4):97-106. doi: 10.1016/0169-328x(94)90036-1.
Morphine not only suppresses norepinephrine-induced increases in LHRH mRNA levels but, in these same animals, it simultaneously amplifies norepinephrine (NE)-induced LH release. These observations suggest that NE may activate parallel mechanisms which independently increase LHRH mRNA levels and LHRH release and suggest that some of these effects could be mediated indirectly via morphine's action on different components of the hypothalamic dopamine (DA) system. Accordingly, in the present studies we examined the effects of morphine on various components of this dopamine system using as our index of altered DA neuronal activity, the changes which occur in tyrosine hydroxylase (TH) mRNA levels following morphine. As an ancillary index of changes which occur in dopamine neuronal activity, we measured, by microdialysis, the changes which occur in preoptic dihydroxyphenylacetic acid (DOPAC) levels after either subcutaneous injections or following microinfusions of morphine into the zona incerta (ZI). In a final study, we evaluated whether DA when given alone (icv infusion) or prior to icv NE would altered LH release. Single cell levels of TH mRNA in preoptic A15 and periventricular anterior hypothalamic A14 DA neurons were not affected by morphine 1, 5 and 24 h later. In contrast, within 1 h after morphine, TH mRNA levels in ZI A13 neurons were significantly elevated and they remained high at 5 nd 24 h compared to controls. Morphine also resulted in a significant rise in TH mRNA levels in tuberoinfundibular DA neurons (TIDA) (A12) within 1 h and these levels remained high to 5 h. Thereafter, by 24 h, message levels had returned to control values. Morphine also resulted in a rapid rise in plasma prolactin (Prl) with peak values occurring at 20 min and then returning to baseline by 90 min. When morphine was given sc it resulted, within 15 min, in a rapid rise in preoptic DOPAC levels and these levels continued to rise such that they were 217% higher than pretreatment values by 105 min. Preoptic 5-hydroxyindoleacetic acid (5-HIAA) levels also increased by 25-75% after sc morphine. The microinfusion of morphine into ZI also resulted in elevated preoptic DOPAC but not 5-HIAA levels within 15 min. The icv infusion of DA alone had no effect on plasma LH whereas, NE (icv) produced a modest but significant increase in plasma LH. When DA was given 15 min prior to the infusion of NE, neither amplification nor inhibition of NE-induced LH release occurred. From these and other studies we conclude that the morphine-induced suppression of TIDA neuronal activity may allow NE to release greater amounts of LHRH from axon terminals in the median eminence.(ABSTRACT TRUNCATED AT 400 WORDS)
吗啡不仅抑制去甲肾上腺素诱导的促性腺激素释放激素（LHRH）mRNA水平的升高，而且在这些相同的动物中，它同时放大去甲肾上腺素（NE）诱导的促黄体生成素（LH）释放。这些观察结果表明，NE可能激活平行机制，这些机制独立地增加LHRH mRNA水平和LHRH释放，并表明其中一些作用可能通过吗啡对下丘脑多巴胺（DA）系统不同成分的作用间接介导。因此，在本研究中，我们以吗啡后酪氨酸羟化酶（TH）mRNA水平的变化作为DA神经元活动改变的指标，研究了吗啡对该多巴胺系统各成分的影响。作为多巴胺神经元活动变化的辅助指标，我们通过微透析测量了皮下注射或向未定带（ZI）微量注射吗啡后视前区二羟基苯乙酸（DOPAC）水平的变化。在最后一项研究中，我们评估了单独给予DA（脑室内注射）或在脑室内注射NE之前给予DA是否会改变LH释放。视前区A15和室周下丘脑前部A14 DA神经元中TH mRNA的单细胞水平在吗啡注射1、5和24小时后不受影响。相反，在吗啡注射后1小时内，ZI A13神经元中的TH mRNA水平显著升高，与对照组相比，在5和24小时时仍保持较高水平。吗啡还导致结节漏斗部DA神经元（TIDA）（A12）中TH mRNA水平在1小时内显著升高，这些水平在5小时内一直保持较高。此后，到24小时时，信息水平已恢复到对照值。吗啡还导致血浆催乳素（Prl）迅速升高，峰值出现在20分钟，然后在90分钟时恢复到基线水平。当皮下注射吗啡时，在15分钟内导致视前区DOPAC水平迅速升高，这些水平持续升高，以至于在105分钟时比预处理值高217%。皮下注射吗啡后视前区5-羟吲哚乙酸（5-HIAA）水平也升高了25 - 75%。向ZI微量注射吗啡在15分钟内也导致视前区DOPAC升高，但5-HIAA水平未升高。单独脑室内注射DA对血浆LH无影响，而NE（脑室内注射）使血浆LH有适度但显著的升高。当在注射NE前15分钟给予DA时，NE诱导的LH释放既没有放大也没有受到抑制。从这些和其他研究中我们得出结论，吗啡诱导的TIDA神经元活动抑制可能使NE从正中隆起的轴突终末释放更多的LHRH。（摘要截短至400字）
