Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine.
Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine.
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DOI：
10.1371/journal.pone.0117601
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Commons KG
中科院分区：
文献类型：
--
作者：
Bajic D;Soiza-Reilly M;Spalding AL;Berde CB;Commons KG
中脑边缘多巴胺能系统的神经可塑性对于与阿片奖励和成瘾相关的行为适应至关重要。这些过程可能受到来自被盖背外侧核（LDTg）的胆碱能传递的影响，LDTg是中脑边缘多巴胺能神经元乙酰胆碱的主要来源。为了研究这种可能性，我们问，如果慢性全身吗啡给药影响基因的表达腹侧和腹外侧水管周围灰质的LDTg水平，使用rtPCR。具体来说，我们使用神经递质和受体PCR阵列在慢性吗啡和生理盐水对照组之间检查了感兴趣区域的基因表达变化。分析表明，慢性吗啡给药导致与胆碱能神经传递相关的基因表达的变化。此外，使用定量免疫荧光技术，我们发现长期吗啡治疗使LDTG神经元中胆碱能标记物（囊泡乙酰胆碱转运蛋白）的免疫标记显着增加。最后，全身给药的非选择性和非竞争性的神经元烟碱拮抗剂美加明（0.5或2毫克/公斤）剂量依赖性阻断表达，并在较小程度上的发展，运动敏化。相同的处理对急性吗啡抗伤害感受、抗伤害感受耐受或对慢性吗啡的依赖没有影响。两者合计，结果表明，内源性烟碱胆碱能神经传递选择性地有助于对吗啡的行为敏化，这一过程可能，在一定程度上，涉及LDTg内的胆碱能神经元。
Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg), a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter) in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg) dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg.
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