Smith C B, Moises H C, Spengler R N, Hollingsworth P J
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Eur J Pharmacol. 1989 Feb 28;161(2-3):111-9. doi: 10.1016/0014-2999(89)90833-9.
The effects of long-term treatment of rats with morphine sulfate were assessed upon the specific binding of [3H]clonidine to alpha 2-adrenoceptors on neural membranes isolated from various brain areas and upon the function of presynaptic alpha 2-adrenoceptors during field stimulation of hippocampal slices. Rats were injected with morphine every 8 h for 14 days with doses which started at 10 mg/kg per injection i.p., and which increased every 3 days to a final dose of 100 mg/kg per injection on the last 2 days. At 8 and 32 h after the last injection the Bmax for [3H]clonidine binding to neural membranes from various brain areas was significantly decreased. At the same times, the fractional release of [3H]noradrenaline during field stimulation of hippocampal slices was increased and the sensitivity of the hippocampal slice to clonidine was reduced which indicated the development of a functional subsensitivity of the presynaptic alpha 2-adrenoceptor. These changes in receptor function persisted at 72 h after the last morphine injection although at this time there were marked increases over control values in [3H]clonidine binding to membranes from all rat brain areas except the caudate nucleus. These findings suggest that changes in alpha 2-adrenoceptor number and function which develop during long-term morphine administration might play an important role in opiate dependence.
评估硫酸吗啡长期治疗大鼠对从不同脑区分离的神经膜上[³H]可乐定与α₂ - 肾上腺素能受体特异性结合的影响，以及在海马切片场刺激期间突触前α₂ - 肾上腺素能受体的功能。大鼠每8小时注射一次吗啡，共14天，起始剂量为腹腔注射每次10 mg/kg，每3天增加一次剂量，在最后2天达到每次100 mg/kg的最终剂量。在最后一次注射后8小时和32小时，[³H]可乐定与不同脑区神经膜结合的Bmax显著降低。同时，海马切片场刺激期间[³H]去甲肾上腺素的释放分数增加，海马切片对可乐定的敏感性降低，这表明突触前α₂ - 肾上腺素能受体出现功能性亚敏感性。尽管在最后一次吗啡注射72小时时，除尾状核外，所有大鼠脑区膜上[³H]可乐定结合量比对照值有显著增加，但受体功能的这些变化仍然存在。这些发现表明，长期给予吗啡期间α₂ - 肾上腺素能受体数量和功能的变化可能在阿片类药物依赖中起重要作用。
