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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Accumbal dopamine, noradrenaline and serotonin activity after naloxone-conditioned place aversion in morphine-dependent mice
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Accumbal dopamine, noradrenaline and serotonin activity after naloxone-conditioned place aversion in morphine-dependent mice

机译：吗啡依赖小鼠中纳洛酮调节的位置厌恶后的累积多巴胺，去甲肾上腺素和5-羟色胺活性

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摘要

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regulation of TH could be involved in the hyperactivity of mesolimbic dopaminergic system observed in morphine-withdrawn mice.
机译：多巴胺（DA）神经元不仅表现出一种信号形式，说明奖励的幅度，延迟和概率，而且还编码负面动机和厌恶事件。除DA以外，其他系统，例如去甲肾上腺素（NA）和5-羟色胺（5-HT），也可能与纳洛酮引起的条件性地方厌恶（CPA;戒断的厌恶后果指数）有关。本研究的目的是评估：（i）伏隔核（NAc）中DA，NA和5-HT的转换，NAv是引起厌恶状态的最重要底物之一，（ii）酪氨酸羟化酶的变化（ TH）基因在腹侧被盖区的表达，以及（iii）纳洛酮诱导的吗啡戒断后NAc中的总TH蛋白水平和TH磷酸化。通过高效液相色谱（HPLC）评估DA，NA和5-HT的转化率。通过实时定量PCR（RT-PCR）确定TH基因表达，并通过Western印迹分析在Ser31和Ser40磷酸化的总TH和TH。目前的结果表明，环境提示与阿片类药物戒断相伴的厌恶情绪高于纳洛酮治疗的生理盐水组，这表明吗啡预处理增强了纳洛酮产生地方厌恶的能力。此外，目前的数据显示，纳洛酮诱导的CPA与NAc中DA和NA转换的增加呈正相关，这与VTA和TH磷酸化中TH基因表达的增加以及NAc中TH蛋白水平的增加平行。因此，本研究表明吗啡依赖性小鼠中纳洛酮引起的厌恶增强了NAc中的DA和NA活性，并暗示TH的转录和转录后调控可能与吗啡戒断所致的中脑边缘多巴胺能系统的过度活跃有关。老鼠。

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