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首页> 外文期刊>The European Journal of Neuroscience >alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate receptor autoradiography in mouse brain after single and repeated withdrawal from diazepam.
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alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate receptor autoradiography in mouse brain after single and repeated withdrawal from diazepam.

机译：从地西epa单次或多次撤药后，小鼠大脑中的α-氨基-3-羟基-5-甲基异恶唑-4-丙酸酯受体放射自显影。

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Withdrawal from chronic treatment with benzodiazepines is associated with increased neuronal excitability leading to anxiety, aversive effects and increased seizure sensitivity. After repeated withdrawal experiences, seizure sensitivity increases while withdrawal-induced anxiety and aversion decrease. We used autoradiographical methods employing [(3)H]Ro48 8587, a selective ligand for glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, to study withdrawal-induced changes in AMPA receptor binding in areas of the mouse brain postulated to be involved in these responses. Mice were given 21 days treatment with diazepam (15 mg/kg, s.c. in sesame oil) followed by withdrawal (single withdrawal) or three blocks of 7 days treatment interspersed with 3-day periods to allow washout of drug (repeated withdrawal). In keeping with heightened excitability in withdrawal from chronic diazepam treatment, the single withdrawal group showed, 72 h after their final dose of diazepam, increased [(3)H]Ro48 8587 binding in several brain areas associated with emotional responses or seizure activity, including hippocampal subfields, amygdalar and thalamic nuclei and motor cortex. In contrast, the repeated withdrawal group showed no changes in [(3)H]Ro48 8587 binding in any brain area studied. These observations are consistent with up-regulation of AMPA receptor-mediated transmission being important in withdrawal-induced anxiety and aversion but not in increased seizure sensitivity associated with repeated withdrawal. As changes in AMPA receptor subunit expression alter the functionality of the receptor, future studies will address this possibility.
机译：从苯二氮卓类药物的慢性治疗中退出会增加神经元兴奋性，从而导致焦虑，厌恶效应和癫痫发作敏感性增加。反复戒断经历后，癫痫发作敏感性增加，而戒断引起的焦虑和反感减少。我们采用了[[3）H] Ro48 8587（一种谷氨酸能α-氨基-3-羟基-5-甲基异恶唑-4-丙酸酯（AMPA）受体的选择性配体）的放射自显影方法，以研究戒断引起的AMPA受体结合变化。假定小鼠大脑区域参与了这些反应。给予小鼠用地西m（21 mg / kg，芝麻油中皮下注射）治疗21天，然后停药（单次停药）或三段7天的治疗，并散布3天的时间以冲洗药物（反复停药）。与长期服用地西epa治疗的退出者兴奋性增强相一致，单次退出者组在他们的最终剂量地西epa后72小时显示，在与情绪反应或癫痫发作相关的多个大脑区域中，[（3）H] Ro48 8587结合增加海马亚区，杏仁核和丘脑核及运动皮层。相反，重复戒断组在所研究的任何脑区域均未显示[（3）H] Ro48 8587结合的变化。这些观察结果与AMPA受体介导的传递的上调在戒断诱发的焦虑和厌恶中起重要作用，但与反复戒断相关的癫痫发作敏感性增加无关。随着AMPA受体亚基表达的变化改变了受体的功能，未来的研究将解决这种可能性。

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