Acute amphetamine exposure selectively desensitizes kappa-opioid receptors in the nucleus accumbens.
Acute amphetamine exposure selectively desensitizes kappa-opioid receptors in the nucleus accumbens.
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急性苯丙胺暴露选择性地使伏隔核中的卡帕阿片受体脱敏。
DOI：
10.1038/sj.npp.1301463
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Hjelmstad,GregoryO
中科院分区：
文献类型：
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作者：
Xia,Yan-fang;He,Li;Whistler,JenniferL;Hjelmstad,GregoryO
在本研究中，我们研究了精神兴奋剂暴露对大鼠中脑边缘系统κ-阿片肽（KOP）受体信号的影响。一个单一的皮下注射安非他明（2.5毫克/公斤）减少KOP受体介导的抑制谷氨酸释放的核壳，作为KOP受体脱敏的结果。这种作用被多巴胺（DA）受体拮抗剂或非选择性阿片受体拮抗剂纳洛酮（1 mg/kg，sc）阻断，并被KOP受体激动剂U69593（0.32 mg/kg，sc）和强啡肽（1 μM）模拟，表明安非他明诱导的强啡肽释放正在产生KOP受体的持久脱敏。尽管事实上，安非他明也增加强啡肽释放腹侧被盖区（VTA），KOP受体在这一地区的功能并没有受到安非他明的影响，有没有差异，在KOP受体介导的变化，放电率或静息膜电位测量VTA神经元从盐水或安非他明治疗的动物。这项研究表明，安非他明可以产生区域选择性适应KOP受体信号，这可能会反过来，改变随后的药物暴露的影响。
In the present study, we investigated the effects of psychostimulant exposure on κ-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (sc) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, sc), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, sc) and dynorphin (1 μM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline-or amphetamine-treated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.