Jin Chunyu, Araki Hiroaki, Nagata Mari, Suemaru Katsuya, Shibata Kazuhiko, Kawasaki Hiromu, Hamamura Takashi, Gomita Yutaka
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1, Tsushima-naka, Okayama, 700-8530, Japan.
Psychopharmacology (Berl). 2004 Oct;175(4):428-35. doi: 10.1007/s00213-004-1844-4.
An opiate antagonist was found to induce motivational withdrawal signs 24 h or even up to 48 h after a single dose of morphine in rats.
The present study was undertaken to determine whether such a withdrawal state would modify the neuronal activity in the brain.
A conditioned place aversion was established following a one-trial paradigm in rats undergoing a single exposure to morphine (10 mg/kg) 24 h prior to naloxone administration (0.5 mg/kg). Subsequently, the expression of the protein product of c-fos gene (c-Fos) following naloxone administration was measured within the extended amygdala.
A significant increase in c-Fos immunoreactivity was seen in the centromedial amygdala (CMA), but not in the bed nucleus of the stria terminalis (BST) and the shell (AcbSh) of the nucleus accumbens (Acb) in rats treated with both morphine and naloxone. Further examination of the distribution of c-Fos-positive neurons along the rostrocaudal axis within CMA showed that the positive neurons distributed throughout this brain area and the caudal level of its central division (the central nucleus of the amygdala, CeA) exhibited the most robust labeling.
Neuronal activity can be increased by naloxone at a dose that produces conditioned place aversion 24 h after a single morphine exposure. CMA, particularly the caudal level of its central division, was of high sensitivity. The current data also suggest a possible involvement of CMA in negative motivational component of precipitated withdrawal from acute morphine dependence.
在大鼠单次注射吗啡后24小时甚至长达48小时，发现一种阿片类拮抗剂可诱发动机性戒断症状。
本研究旨在确定这种戒断状态是否会改变大脑中的神经元活动。
在给予纳洛酮（0.5mg/kg）前24小时，对大鼠进行单次吗啡（10mg/kg）暴露，采用单次试验范式建立条件性位置厌恶。随后，在扩展杏仁核内测量纳洛酮给药后c-fos基因（c-Fos）蛋白质产物的表达。
在同时接受吗啡和纳洛酮治疗的大鼠中，中央内侧杏仁核（CMA）中c-Fos免疫反应性显著增加，但终纹床核（BST）和伏隔核（Acb）壳部（AcbSh）中未增加。进一步检查CMA内沿前后轴的c-Fos阳性神经元分布，发现阳性神经元分布于整个脑区，其中央部（杏仁核中央核，CeA）的尾部水平标记最为明显。
纳洛酮可在单次吗啡暴露后24小时产生条件性位置厌恶的剂量下增加神经元活动。CMA，特别是其中央部的尾部水平，具有高敏感性。目前的数据还表明，CMA可能参与了急性吗啡依赖戒断时负性动机成分的形成。
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