Cicero T J, Nock B, O'Connor L
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
J Pharmacol Exp Ther. 1993 Jan;264(1):47-53.
Morphine and naloxone exert age-dependent effects on secretion of luteinizing hormone (LH) in the male rat. Morphine suppresses LH secretion at very early stages of development, well before puberty, whereas naloxone does not increase LH until after puberty. The mechanisms underlying these age-dependent effects of opiates on the hypothalamic-pituitary-gonadal axis in pre- and postpubertal rats are poorly understood at the present time. The purpose of the present studies was to examine one plausible explanation of these effects: that morphine and naloxone act through different receptors in the pubescent male rat than they do in adults to influence LH secretion. Specifically, we examined whether naloxone blocks the effects of morphine on LH in prepubescent and adult rats which would be anticipated if both drugs were exerting their effects on LH via the same opiate receptor. Surprisingly, we found that naloxone did not reverse the effects of morphine on serum LH levels in the prepubescent animal, although it fully reversed this effect in adults. This non-naloxone-reversible effect of morphine appeared to be specific to LH, since naloxone antagonized morphine's effects on several other hormones (e.g., prolactin and corticosterone) and completely attenuated morphine's antinociceptive activity in prepubescent rats. Additionally, naloxone precipitated a withdrawal syndrome in the prepubescent morphine-dependent animal that was quantitatively and qualitatively the same as in adults.(ABSTRACT TRUNCATED AT 250 WORDS)
吗啡和纳洛酮对雄性大鼠促黄体生成素(LH)的分泌具有年龄依赖性影响。在发育的早期阶段,即青春期之前,吗啡会抑制LH的分泌,而纳洛酮直到青春期后才会增加LH的分泌。目前,对于青春期前和青春期后大鼠中阿片类药物对下丘脑 - 垂体 - 性腺轴的这些年龄依赖性影响的潜在机制了解甚少。本研究的目的是检验对这些影响的一种合理的解释:即吗啡和纳洛酮在青春期雄性大鼠中作用于与成年大鼠不同的受体来影响LH的分泌。具体而言,我们研究了纳洛酮是否会阻断吗啡对青春期前和成年大鼠LH的影响,如果两种药物都通过相同的阿片受体对LH发挥作用,那么这种情况是可以预期的。令人惊讶的是,我们发现纳洛酮并不能逆转吗啡对青春期前动物血清LH水平的影响,尽管它能完全逆转成年动物中的这种影响。吗啡的这种非纳洛酮可逆效应似乎对LH具有特异性,因为纳洛酮能拮抗吗啡对其他几种激素(如催乳素和皮质酮)的影响,并完全减弱吗啡在青春期前大鼠中的抗伤害感受活性。此外,纳洛酮在青春期前依赖吗啡的动物中引发了戒断综合征,其在数量和质量上与成年动物相同。(摘要截断于250字)