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大鼠经典厌恶条件反射习得与消退过程中内侧前额叶皮质和腹侧纹状体多巴胺释放的解离

Dissociations in dopamine release in medial prefrontal cortex and ventral striatum during the acquisition and extinction of classical aversive conditioning in the rat.

作者信息

Wilkinson L S, Humby T, Killcross A S, Torres E M, Everitt B J, Robbins T W

机构信息

The Babraham Institute, Department of Neurobiology, Cambridge, UK.

出版信息

Eur J Neurosci. 1998 Mar;10(3):1019-26. doi: 10.1046/j.1460-9568.1998.00119.x.

Abstract

Dual perfusion in vivo brain microdialysis was used to monitor extracellular levels of dopamine in the medial prefrontal cortex and ventral striatum during the acquisition and extinction of a classical aversive conditioning paradigm in rats. The main finding was a dissociation in the pattern of release in the two brain areas. The first stimulus-footshock pairing elicited large increases in cortical dopamine over baseline levels that were much greater than the increases elicited by different stimuli of equivalent salience that were unpaired with footshock. In contrast, dopamine levels in ventral striatum were unchanged under these conditions. Over the next two pairings, there was a decline in the cortical response and an increase in the response in ventral striatum. The first presentation of the aversive conditioned stimulus in a separate context elicited the largest response in ventral striatum. Post-conditioning, the cortical response to the conditioned stimulus was smaller than that elicited by the initial stimulus-footshock pairing and was equivalent in magnitude to that elicited by stimuli unpaired with footshock. Over the final two conditioned stimuli presentations, in the absence of the footshock reinforcer (extinction), responses declined in both brain areas. Simultaneous monitoring of behaviour indicated that the neurochemical events were accompanied by effective aversive learning, as indexed by conditioned freezing responses. The data are discussed in terms of the hypothesis that medial prefrontal cortex is especially engaged during novel circumstances which may, potentially, require new learning, whilst ventral striatal dopamine more closely follows the expression of conditioned responding during learning and extinction.

摘要

采用双灌注体内脑微透析技术,在大鼠经典厌恶性条件反射范式的习得和消退过程中,监测内侧前额叶皮质和腹侧纹状体中多巴胺的细胞外水平。主要发现是两个脑区释放模式的分离。第一次刺激-电击配对引起皮质多巴胺水平比基线水平大幅升高,这比与电击未配对的同等显著性的不同刺激所引起的升高要大得多。相比之下,在这些条件下腹侧纹状体中的多巴胺水平没有变化。在接下来的两次配对中,皮质反应下降,腹侧纹状体反应增加。在单独情境中首次呈现厌恶性条件刺激时,腹侧纹状体反应最大。条件反射后,皮质对条件刺激的反应小于最初刺激-电击配对所引起的反应,且幅度与未与电击配对的刺激所引起的反应相当。在最后两次条件刺激呈现过程中,在没有电击强化物(消退)的情况下,两个脑区的反应均下降。行为的同步监测表明,神经化学事件伴随着有效的厌恶性学习,以条件性僵住反应为指标。根据内侧前额叶皮质在可能需要新学习的新情境中特别活跃,而腹侧纹状体多巴胺在学习和消退过程中更紧密地跟随条件反应表达的假设,对这些数据进行了讨论。

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