Accumbal dopamine, noradrenaline and serotonin activity after naloxone-conditioned place aversion in morphine-dependent mice
Accumbal dopamine, noradrenaline and serotonin activity after naloxone-conditioned place aversion in morphine-dependent mice
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DOI：
10.1016/j.neuint.2012.06.011
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发表时间：
2012-08-01
影响因子：
4.2
通讯作者：
Luisa Laorden, M.
中科院分区：
文献类型：
--
作者：
Gomez-Milanes, Ivan;Almela, Pilar;Luisa Laorden, M.
多巴胺(DA)神经元不仅表现出一种模式，指示奖励的大小、延迟和概率，而且还编码负面动机和厌恶事件。除DA外，其他系统，如去甲肾上腺素(NA)和5-羟色胺(5-HT)也可能与纳洛酮诱导的条件性位置厌恶(CPA；戒断厌恶后果的指数)有关。本研究旨在观察吗啡戒断后伏隔核(NAC)DA、NA和5-羟色胺(5-HT)代谢的变化，以及腹侧被盖区酪氨酸羟化酶(TH)基因表达的变化。用高效液相色谱法测定DA、NA和5-羟色胺的转化率。用实时定量聚合酶链式反应(RT-PCR)检测TH基因的表达，用Western印迹法检测Ser31和Ser40磷酸化的总TH和TH。目前的结果表明，与阿片类药物戒断相结合的环境线索的厌恶程度高于纳洛酮盐水组，这表明吗啡预处理增强了纳洛酮产生位置厌恶的能力。此外，目前的数据表明，纳洛酮诱导的CPA与NAc中DA和NA周转的增加呈正相关，这与VTA中TH基因表达的增加和NAC中TH的磷酸化和TH蛋白水平的提高平行。因此，本研究表明，纳洛酮诱导的吗啡依赖小鼠的厌恶感增强了NAc中DA和NA的活性，提示TH的转录和转录后调节可能参与了吗啡戒断小鼠中脑边缘多巴胺能系统的过度活动。(C)2012爱思唯尔有限公司。保留所有权利。
Dopamine (DA) neurons not only show a pattern signaling the magnitude, delay and probability of rewards but also code negative motivation and aversive events. Beside DA, other systems such as noradrenaline (NA) and serotonin (5-HT) may also be implicated in naloxone-induced conditioned place aversion (CPA; an index of the aversive consequences of withdrawal). The purpose of the present study was to evaluate: (i) the turnover of DA, NA and 5-HT in the nucleus accumbens (NAc), one of the most important substrates for aversive states, (ii) the changes in tyrosine hydroxylase (TH) gene expression in the ventral tegmental area, and (iii) total TH protein levels and TH phosphorylation in the NAc after naloxone-induced morphine withdrawal. DA, NA and 5-HT turnover was evaluated by high-performance liquid chromatography (HPLC). TH gene expression was determined by real time quantitative PCR (RT-PCR) and total TH and TH phosphorylated at Ser31 and Ser40 were analyzed by Western blot. Present results show that the aversion for environmental cues paired with opioid withdrawal was higher than that observed in the saline group treated with naloxone, which indicates that morphine pretreatment potentiated the ability of naloxone to produce place aversion. In addition, present data show that naloxone-induced CPA positively correlated with an increase of DA and NA turnover in the NAc, which paralleled an increase in TH gene expression in the VTA and TH phosphorylation and enhanced TH protein levels in the NAc. Thus, the present study indicates that naloxone-induced aversion in morphine-dependent mice enhances DA and NA activity in the NAc and suggests that transcriptional and post-transcriptional regulation of TH could be involved in the hyperactivity of mesolimbic dopaminergic system observed in morphine-withdrawn mice. (C) 2012 Elsevier Ltd. All rights reserved.