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冲动型大鼠在延迟折扣任务中表现出多巴胺释放动力学的迟钝,与可卡因史无关。

Impulsive Rats Exhibit Blunted Dopamine Release Dynamics during a Delay Discounting Task Independent of Cocaine History.

机构信息

Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC 27599.

出版信息

eNeuro. 2017 Apr 24;4(2). doi: 10.1523/ENEURO.0119-17.2017. eCollection 2017 Mar-Apr.

Abstract

The inability to wait for a large, delayed reward when faced with a small, immediate one, known as delay discounting, has been implicated in a number of disorders including substance abuse. Individual differences in impulsivity on the delay discounting task are reflected in differences in neural function, including in the nucleus accumbens (NAc) core. We examined the role of a history of cocaine self-administration, as well as individual differences in impulsivity, on rapid dopamine (DA) release dynamics in the NAc core. Rats with a history of cocaine or water/saline self-administration were tested on delay discounting while being simultaneously assayed for rapid DA release using electrochemical methods. In controls, we found that cue DA release was modulated by reward delay and magnitude, consistent with prior reports. A history of cocaine had no effect on either delay discounting or DA release dynamics. Nonetheless, independent of drug history, individual differences in impulsivity were related to DA release in the NAc core. First, high impulsive animals exhibited dampened cue DA release during the delay discounting task. Second, reward delay and magnitude in high impulsive animals failed to robustly modulate changes in cue DA release. Importantly, these two DAergic mechanisms were uncorrelated with each other and, together, accounted for a high degree of variance in impulsive behavior. Collectively, these findings demonstrate two distinct mechanisms by which rapid DA signaling may influence impulsivity, and illustrate the importance of NAc core DA release dynamics in impulsive behavior.

摘要

当面对小的即时奖励而无法等待大的延迟奖励时,这种被称为延迟折扣的能力,与多种障碍有关,包括物质滥用。在延迟折扣任务中的冲动个体差异反映在神经功能的差异上,包括伏隔核(NAc)核心。我们研究了可卡因自我给药史以及冲动性个体差异对 NAc 核心中快速多巴胺(DA)释放动力学的作用。具有可卡因或水/盐水自我给药史的大鼠在进行延迟折扣测试的同时,使用电化学方法同时检测快速 DA 释放。在对照组中,我们发现线索 DA 释放受到奖励延迟和大小的调节,这与之前的报告一致。可卡因史对延迟折扣或 DA 释放动力学没有影响。尽管如此,冲动性个体差异与 NAc 核心中的 DA 释放有关,而与药物史无关。首先,高冲动动物在延迟折扣任务中表现出线索 DA 释放减弱。其次,高冲动动物的奖励延迟和大小未能强烈调节线索 DA 释放的变化。重要的是,这两种多巴胺能机制彼此不相关,并且共同解释了冲动行为的高度可变性。总的来说,这些发现表明快速 DA 信号可能影响冲动性的两种不同机制,并说明了 NAc 核心 DA 释放动力学在冲动行为中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8db2/5402299/9b54a528ff98/enu0021722920001.jpg

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