The role of endogenous dynorphin in ethanol-induced state-dependent CPP.
The role of endogenous dynorphin in ethanol-induced state-dependent CPP.
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DOI：
10.1016/j.bbr.2011.10.035
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发表时间：
2012-02-01
影响因子：
2.7
通讯作者：
Lutfy K
中科院分区：
文献类型：
--
作者：
Nguyen K;Tseng A;Marquez P;Hamid A;Lutfy K
本研究旨在探讨内源性强啡肽/κ阿片受体（DYN/KOP）系统在乙醇诱导的状态依赖性条件性位置偏爱（CPP）中的作用。为此，在第1天测试缺乏pro-DYN基因的小鼠及其野生型同窝小鼠/对照的基线位置偏好，连续三天每天用盐水或乙醇（2g/kg）接受15分钟的早晨和下午调节，然后在第5天在无药物状态下测试CPP，并在第8天在盐水或乙醇（1或2g/kg）激发后测试CPP。考虑到基因敲除小鼠可能发生代偿性发育变化，还在野生型小鼠中研究了KOP拮抗剂nor-binaltorphimine（nor-BNI）对乙醇诱导的状态依赖性CPP的影响。在第1天，测试小鼠的基线位置偏好，4小时后，用盐水或去甲-BNI（10 mg/kg）处理。在第2-4天，小鼠接受15分钟的上午和下午的调节，并在第5天在无药物状态下和第8天在乙醇（1 g/kg）激发后测试CPP。在缺乏pro-DYN基因的小鼠及其野生型同窝仔/对照组以及用nor-BNI处理的野生型小鼠及其盐水处理的对照组中观察到相当的CPP。然而，这些小鼠相比，其各自的控制表现出更大的CPP响应后，乙醇（1克/公斤）的挑战，这表明内源性DYN/KOP系统可能负调节乙醇诱导的状态依赖性CPP。
The aim of this study was to determine the role of the endogenous dynorphin/kappa opioid receptor (DYN/KOP) system in ethanol-induced state-dependent conditioned place preference (CPP). To this end, mice lacking the pro-DYN gene and their wild-type littermates/controls were tested for baseline place preference on day 1, received 15-min morning and afternoon conditionings with saline or ethanol (2 g/kg) each day for three consecutive days and were then tested for CPP under a drug-free state on day 5 and following a saline or ethanol (1 or 2 g/kg) challenge on day 8. Given that compensatory developmental changes may occur in knockout mice, the effect of nor-binaltorphimine (nor-BNI), a KOP antagonist, on state-dependent CPP induced by ethanol was also studied in wild-type mice. On day 1, mice were tested for baseline place preference and, 4 h later, treated with saline or nor-BNI (10 mg/kg). On days 2–4, mice received 15-min morning and afternoon conditionings and were tested for CPP under a drug-free state on day 5 and following an ethanol (1 g/kg) challenge on day 8. A comparable CPP was observed in mice lacking the pro-DYN gene and their wild-type littermates/controls as well as in wild-type mice treated with nor-BNI and their saline-treated controls. However, these mice compared to their respective controls exhibited a greater CPP response following an ethanol (1 g/kg) challenge, suggesting that the endogenous DYN/KOP system may negatively regulate ethanol-induced state-dependent CPP.