Electrophysiological responsiveness to isoproterenol in rat hippocampal slices correlates with changes in beta-adrenergic receptor density induced by chronic morphine treatment.

Electrophysiological responsiveness to isoproterenol in rat hippocampal slices correlates with changes in beta-adrenergic receptor density induced by chronic morphine treatment.
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大鼠海马切片对异丙肾上腺素的电生理反应与慢性吗啡治疗引起的β-肾上腺素能受体密度的变化相关。

DOI:
10.1016/0006-8993(89)90667-7
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发表时间:
1989
期刊:
影响因子:
2.9
通讯作者:
Smith,CB
Smith,CB
中科院分区:
医学3区
文献类型:
--
作者:
Moises,HC;Smith,CB

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本实验观察了慢性吗啡处理和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天的慢性治疗导致海马中β-肾上腺素能受体数量增加19%,这是通过特异性拮抗剂[3 H]二氢阿普洛尔(DHA)的结合来测量的。相比之下,[3 H]DHA的特异性结合位点的数量减少了27%,在海马在吗啡戒断动物,与盐水治疗的对照组相比。β-肾上腺素能受体密度的这些变化并不伴随[3 H]DHA的解离常数(Kd)或去甲肾上腺素或异丙肾上腺素置换[3 H]拮抗剂的抑制常数(Ki)的显著变化。在体外海马脑片制备的电生理实验表明,响应阈值以及最大浓度的异丙肾上腺素显着增强吗啡依赖的动物,与对照组相比,而电生理反应的最大浓度的异丙肾上腺素减少吗啡戒断大鼠的切片。本研究结果表明,海马β-肾上腺素能受体在吗啡依赖过程中表达上调,而在阿片戒断过程中表达下调。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β-肾上腺素能受体激动剂的电生理反应性的相应增加和减少。
The effects of chronic morphine treatment and morphine withdrawal on β-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 β-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 In comparison, the number of specific binding sites for [3H]DHA was decreased 27% in hippocampus in morphine-withdrawn animals, compared to saline-treated controls.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 β-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electrophysiological responsiveness to maximal concentrations of isoproterenol was decreased in slices from morphine-withdrawn rats.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 β-adrenergic receptors in hippocampus are up-regulated during the development of morphine dependence and down-regulated during opiate withdrawal. These changes in hippocampal β-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 β-adrenergic receptor agonist.
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