Bartolome M B, Kuhn C M
Eur J Pharmacol. 1983 Nov 25;95(3-4):231-8. doi: 10.1016/0014-2999(83)90639-8.
The effects of methadone (METH) on serum levels of prolactin (PRL), growth hormone (GH), corticosterone (CS), TSH and T4 were determined in male and female rats. METH initially (15-45 min after injection) decreased TSH and increased PRL, GH and CS in both male and female rats. These changes were followed by a rebound decrease in CS and increase in TSH 4 h after METH administration. METH decreased GH at 0.1 mg/kg, but increased secretion with doses of 0.5 mg/kg and higher. Changes in PRL, CS and TSH were only seen with 1 mg/kg and higher. Naloxone blocked increases in serum GH, PRL and CS and the decrease in TSH caused by METH. Serum PRL increased significantly more in females than in males, although other endocrine actions of METH were the same in males and females. Pretreatment of animals with METH 4 h before a second challenge dose did not affect TSH, PRL or GH responses to METH. However, peak CS levels were lower in pretreated animals than in controls. These findings demonstrate that METH elicits a complex profile of endocrine response which probably reflects actions at multiple receptor and/or anatomical sites, and suggest that reported sex differences in METH metabolism are not limiting in determining the hormonal response to this drug. These results also suggest that single-dose tolerance develops to the effects of METH on CS but not on other endocrine parameters.
研究了美沙酮（METH）对雄性和雌性大鼠血清催乳素（PRL）、生长激素（GH）、皮质酮（CS）、促甲状腺激素（TSH）和甲状腺素（T4）水平的影响。美沙酮最初（注射后15 - 45分钟）会降低雄性和雌性大鼠的TSH，并升高PRL、GH和CS。给药4小时后，这些变化之后会出现CS的反弹下降和TSH的升高。0.1mg/kg的美沙酮会降低GH，但0.5mg/kg及更高剂量会增加GH分泌。只有1mg/kg及更高剂量时才会出现PRL、CS和TSH的变化。纳洛酮可阻断美沙酮引起的血清GH、PRL和CS升高以及TSH降低。虽然美沙酮的其他内分泌作用在雄性和雌性中相同，但血清PRL在雌性中升高幅度明显大于雄性。在第二次给予挑战剂量前4小时用美沙酮预处理动物，不影响TSH、PRL或GH对美沙酮的反应。然而，预处理动物的CS峰值水平低于对照组。这些发现表明，美沙酮引发了复杂的内分泌反应谱，这可能反映了其在多个受体和/或解剖部位的作用，并表明报告的美沙酮代谢中的性别差异在决定对该药物的激素反应方面并无限制。这些结果还表明，单次给药耐受性会发展至美沙酮对CS的作用，但对其他内分泌参数则不会。
