Moises H C, Smith C B
Department of Physiology, University of Michigan, Ann Arbor 48109.
Brain Res. 1989 Apr 17;485(1):67-78. doi: 10.1016/0006-8993(89)90667-7.
The effects of chronic morphine treatment and morphine withdrawal on beta-adrenergic receptor density and electrophysiological responsiveness in rat hippocampus were examined. Chronic treatment of rats with morphine for 14 days resulted in a 19% increase in the number of beta-adrenergic receptors in hippocampus, as measured by the binding of the specific antagonist [3H]dihydroalprenolol (DHA). In comparison, the number of specific binding sites for [3H]DHA was decreased 27% in hippocampus in morphine-withdrawn animals, compared to saline-treated controls. These alterations in beta-adrenergic receptor density were not accompanied by a significant change in the dissociation constant (Kd) for [3H]DHA or in the inhibitory constants (Ki) for the displacement of the [3H]-antagonist by either norepinephrine or isoproterenol. Electrophysiological experiments in the in vitro hippocampal slice preparation revealed that responses to threshold as well as maximal concentrations of isoproterenol were significantly enhanced in morphine-dependent animals, compared to controls, whereas electrophysiological responsiveness to maximal concentrations of isoproterenol was decreased in slices from morphine-withdrawn rats. The results of this study indicate that beta-adrenergic receptors in hippocampus are up-regulated during the development of morphine dependence and down-regulated during opiate withdrawal. These changes in hippocampal beta-adrenergic receptor density are likely to be of functional relevance since they are manifested in a corresponding increase and decrease, respectively, in electrophysiological responsiveness to an exogenously administered beta-adrenergic receptor agonist.
研究了慢性吗啡治疗及吗啡戒断对大鼠海马β-肾上腺素能受体密度和电生理反应性的影响。用吗啡对大鼠进行14天的慢性治疗后，通过特异性拮抗剂[³H]二氢阿普洛尔（DHA）的结合测定，海马中β-肾上腺素能受体数量增加了19%。相比之下，与生理盐水处理的对照组相比，吗啡戒断动物海马中[³H]DHA的特异性结合位点数量减少了27%。β-肾上腺素能受体密度的这些变化并未伴随着[³H]DHA解离常数（Kd）或去甲肾上腺素或异丙肾上腺素对[³H]拮抗剂置换的抑制常数（Ki）的显著变化。体外海马脑片制备的电生理实验表明，与对照组相比，吗啡依赖动物对阈值以及最大浓度异丙肾上腺素的反应显著增强，而吗啡戒断大鼠脑片对最大浓度异丙肾上腺素的电生理反应性降低。本研究结果表明，海马中的β-肾上腺素能受体在吗啡依赖形成过程中上调，在阿片类药物戒断过程中下调。海马β-肾上腺素能受体密度的这些变化可能具有功能相关性，因为它们分别表现为对外源性给予的β-肾上腺素能受体激动剂的电生理反应性相应增加和降低。
