The endocannabinoid system regulates synaptic transmission in nucleus accumbens by increasing DAGL-α expression following short-term morphine withdrawal1
The endocannabinoid system regulates synaptic transmission in nucleus accumbens by increasing DAGL-α expression following short-term morphine withdrawal1
复制标题
内源性大麻素系统通过短期吗啡戒断后增加 DAGL-α 表达来调节伏隔核中的突触传递1
DOI：
10.1111/bph.12969
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Guo-Dong G
中科院分区：
文献类型：
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作者：
Xing-Qin Wang;Jie Ma;Wei Cui;Wei-Xin Yuan;Gang Zhu;Qian Yang;Li-Jun Heng;Guo-Dong G
背景与目的内源性大麻素（endocannabinoid，eCB）系统参与调节药物成瘾的通路，其介导的突触可塑性与成瘾行为有关。本研究采用条件位置偏爱（CPP）技术，探讨吗啡短期戒断后大鼠丘脑核团（NAcc）eCB依赖性突触可塑性变化的分子机制。使用全细胞膜片钳记录测量NAcc中中等棘神经元的诱发抑制性突触后电流。评估了NAcc中去极化诱导的抑制抑制（DSI）的变化，以确定短期吗啡戒断对eCB系统的影响。为探讨短期吗啡戒断对eCB系统的潜在调节机制，采用Western blot方法检测eCB系统中甘油二酯脂肪酶α（DGL-α）和甘油单酯脂肪酶（monoacylglycerol lipase，monoacylglycerol lipase。与生理盐水组相比，短期吗啡戒断后大鼠NAcc中的DSI水平显著增加。此外，DSI的增加与DGL-α表达的显著增加相一致。结论和意义短期吗啡戒断增强了NAcc中抑制性突触传递的eCB调制。我们还发现，短期吗啡戒断后DGL-α表达升高，这表明eCB 2-花生四烯酰甘油而不是花生四烯酰胺介导了DSI的增加。这些发现为药物成瘾期间NAcc中eCB介导的可塑性机制提供了有用的见解。链接文章这篇文章是内源性大麻素主题部分的一部分。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc
Background and PurposeThe endocannabinoid (eCB) system is involved in pathways that regulate drug addiction and eCB‐mediated synaptic plasticity has been linked with addictive behaviours. Here, we investigated the molecular mechanisms underlying the changes in eCB‐dependent synaptic plasticity in the nucleus accumbens core (NAcc) following short‐term withdrawal from repeated morphine treatment.Experimental ApproachConditioned place preference (CPP) was used to evaluate the rewarding effects of morphine in rats. Evoked inhibitory postsynaptic currents of medium spiny neurons in NAcc were measured using whole‐cell patch‐clamp recordings. Changes in depolarization‐induced suppression of inhibition (DSI) in the NAcc were assessed to determine the effect of short‐term morphine withdrawal on the eCB system. To identify the potential modulation mechanism of short‐term morphine withdrawal on the eCB system, the expression of diacylglycerol lipase α (DGL‐α) and monoacylglycerol lipase was detected by Western blot analysis.Key ResultsRepeated morphine administration for 7 days induced stable CPP. Compared with the saline group, the level of DSI in the NAcc was significantly increased in rats after short‐term morphine withdrawal. Furthermore, this increase in DSI coincided with a significant increase in the expression of DGL‐α.Conclusions and ImplicationsShort‐term morphine withdrawal potentiates eCB modulation of inhibitory synaptic transmission in the NAcc. We also found that DGL‐α expression was elevated after short‐term morphine withdrawal, suggesting that the eCB 2‐arachidonyl‐glycerol but not anandamide mediates the increase in DSI. These findings provide useful insights into the mechanisms underlying eCB‐mediated plasticity in the NAcc during drug addiction.Linked ArticlesThis article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc