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在十个月的时间里,适度摄入乙醇会导致 Wistar 大鼠纹状体活动的区域特异性抑制。

Region-specific depression of striatal activity in Wistar rat by modest ethanol consumption over a ten-month period.

机构信息

Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, PO Box 410, 405 30 Gothenburg, Sweden.

出版信息

Alcohol. 2013 Jun;47(4):289-98. doi: 10.1016/j.alcohol.2013.03.003. Epub 2013 Apr 17.

Abstract

The nucleus accumbens (nAc) is the primary target for the mesolimbic dopamine system and a key brain region for the reinforcing effects displayed by drugs of abuse, including ethanol. During the transition from recreational to compulsive consumption of reinforcing drugs, however, the dorsal striatum seems to be recruited. Understanding how synaptic activity is altered in a sub-region specific manner in the striatum during the course of long-term drug consumption thus could be essential for understanding the long-lasting changes produced by addictive substances, including ethanol. Here we evaluated synaptic activity in the dorsolateral striatum (DLS) and ventral striatum (nucleus accumbens, nAc) of single-housed Wistar rats consuming water, or water and ethanol, for up to 10 months. Even though ethanol intake was moderate, it was sufficient to decrease input/output function in response to stimulation intensity in the DLS, while recorded population spike (PS) amplitudes in the nAc were unaffected. Striatal disinhibition induced by the GABAA receptor antagonist bicuculline had a slower onset in rats that had consumed ethanol for 2 months, and was significantly depressed in slices from rats that had consumed ethanol for 4 months. Bicuculline-induced disinhibition in the nAc, on the other hand, was not significantly altered by long-term ethanol intake. Changes in PS amplitude induced by taurine or the glycine receptor antagonist strychnine were not significantly altered by ethanol in any brain region. Even though input/output function was not significantly affected by age, there was a significant decline in antagonist-induced disinhibition in brain slices from aged rats. The data presented here suggest that even modest consumption of ethanol is sufficient to alter neurotransmission in the striatum, while synaptic activity appears to be relatively well-preserved in the nAc during the course of long-term ethanol consumption.

摘要

伏隔核(nAc)是中脑边缘多巴胺系统的主要靶标,也是包括乙醇在内的成瘾药物显示强化作用的关键大脑区域。然而,在从娱乐性使用到强迫性使用强化药物的转变过程中,背侧纹状体似乎被招募了。因此,了解在长期药物消费过程中纹状体的特定亚区的突触活动如何发生改变,对于理解包括乙醇在内的成瘾物质产生的持久变化可能是至关重要的。在这里,我们评估了长期(长达 10 个月)摄入水或水和乙醇的单笼饲养 Wistar 大鼠的背外侧纹状体(DLS)和腹侧纹状体(伏隔核,nAc)中的突触活动。尽管乙醇摄入量适中,但足以降低 DLS 中刺激强度的输入/输出功能,而 nAc 中的记录群体锋电位(PS)幅度不受影响。GABAA 受体拮抗剂荷包牡丹碱诱导的纹状体抑制作用在摄入乙醇 2 个月的大鼠中出现较慢的起始,并且在摄入乙醇 4 个月的大鼠的切片中显著抑制。另一方面,长期乙醇摄入并未显著改变 nAc 中荷包牡丹碱诱导的抑制作用。牛磺酸或甘氨酸受体拮抗剂士的宁诱导的 PS 幅度变化在任何脑区均未因乙醇而显著改变。尽管输入/输出功能不受年龄的显著影响,但在老年大鼠的脑片中,拮抗剂诱导的抑制作用显著下降。这里呈现的数据表明,即使适度摄入乙醇也足以改变纹状体中的神经传递,而在长期乙醇摄入过程中,nAc 中的突触活动似乎相对较好地保留下来。

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