Effect of chronic naltrexone and methadone administration on brain immunoreactive beta-endorphin in the rat.
Effect of chronic naltrexone and methadone administration on brain immunoreactive beta-endorphin in the rat.
复制标题
长期纳曲酮和美沙酮给药对大鼠脑免疫反应性β-内啡肽的影响。
作者：
V. V. Ragavan;S. Wardlaw;M. Kreek;A. Frantz
研究了美沙酮（一种长效阿片激动剂）和纳洛酮（一种长效阿片拮抗剂）长期治疗对大鼠脑免疫反应性β-内啡肽（IR-β-EP）浓度的影响。雄性大鼠接受美沙酮（2.5 mg/kg/天）、纳洛酮（2 mg/kg/天）或生理盐水治疗30天。在重复实验中，大鼠接受美沙酮2.5 mg/kg/天、纳洛酮4 mg/kg/天或生理盐水治疗36天。将脑区域在0.2 N HCl中匀浆，并通过RIA测定IR-β-EP。美沙酮治疗后，在两项实验中均未测量到下丘脑、丘脑、中脑或杏仁核的IR-β-EP含量变化。然而，在两个实验中，纳洛酮显著降低了大脑IR-β-EP。在第一项研究中，下丘脑IR-β-EP从189 +/- 17（SEM）下降到纳洛酮治疗后的132 +/- 7.0 ng/g组织湿重（p <0.01）。在第二个实验中，纳洛酮将下丘脑中的IR-β-EP从23.4 +/- 3.6降低到15.5 +/- 1.2 ng/mg蛋白（p <0.005）。丘脑（从6.74 +/- 0.59到4.59 +/- 0.38 ng/mg蛋白）和杏仁核（从1.31 +/- 0.08到0.90 +/- 0.10）的IR-β-EP含量也有类似的降低（p <0.01）。我们的结论是，阿片受体的阿片拮抗剂的占用降低脑IR-β-EP的水平，并表明，慢性阿片受体阻滞剂可能会导致脑β-EP释放的代偿性增加。
The effects of chronic treatment with methadone, a long-acting opiate agonist, and naltrexone, a long-acting opiate antagonist on brain immunoreactive beta-endorphin (IR-beta-EP) concentrations were studied in the rat. Male rats were treated for 30 days with either methadone, 2.5 mg/kg/day; naltrexone 2 mg/kg/day, or saline. In a repeat experiment, rats were treated for 36 days with either methadone 2.5 mg/kg/day; naltrexone 4 mg/kg/day, or saline. Brain regions were homogenized in 0.2 N HCl and assayed for IR-beta-EP by RIA. No change in the IR-beta-EP content of the hypothalamus, thalamus, midbrain, or amygdala was measured in either experiment after methadone treatment. Naltrexone, however, significantly lowered brain IR-beta-EP in both experiments. In the first study hypothalamic IR-beta-EP fell from 189 +/- 17 (SEM) to 132 +/- 7.0 ng/g wet weight of tissue after naltrexone treatment (p less than 0.01). In the second experiment naltrexone lowered IR-beta-EP in the hypothalamus from 23.4 +/- 3.6 to 15.5 +/- 1.2 ng/mg protein (p less than 0.005). Similar decreases in the IR-beta-EP content of the thalamus (from 6.74 +/- 0.59 to 4.59 +/- 0.38 ng/mg protein) and amygdala (from 1.31 +/- 0.08 to 0.90 +/- 0.10) were also measured (p less than 0.01). We conclude that occupancy of opiate receptors by an opiate antagonist reduces brain levels of IR-beta-EP and suggests that chronic opiate receptor blockade may result in a compensatory increase in brain beta-EP release.