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从血清素受体基因敲除小鼠看冲动行为的神经生物学见解

Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice.

作者信息

Brunner D, Hen R

机构信息

Department of Developmental Psychobiology, Columbia University, New York, New York 10032, USA.

出版信息

Ann N Y Acad Sci. 1997 Dec 29;836:81-105. doi: 10.1111/j.1749-6632.1997.tb52356.x.

Abstract

Although the concept of impulsivity has proved useful in human and animal studies of addiction, violent aggression, and violent suicide, and has been recognized as an important component of human behavior, little research has been done to understand the underlying psychobiological mechanisms. We explore the concept of impulsivity and its relation with the neurotransmitter serotonin in the context of aggressive behavior and behavior associated with positive reinforcement using a knockout mouse that lacks one of the serotonin receptors, the 5-HT1B receptor. This knockout mouse shows more impulsive aggression, acquires cocaine self-administration faster, and drinks more alcohol than the corresponding wild-type control. We show that the impulsive characteristics of these mice are not due to change in cognitive functions: in a cognitive task involving a choice between a small immediate one and a larger more delayed reward, knockout mice showed intact choice and timing capabilities and good discrimination of reward amounts. Thus, this mouse may prove an animal model of addiction and motor impulsivity.

摘要

尽管冲动性这一概念已被证明在人类和动物的成瘾、暴力攻击及暴力自杀研究中很有用,并且已被视为人类行为的一个重要组成部分,但对于理解其潜在的心理生物学机制,人们却很少开展研究。我们使用一种敲除了5-羟色胺(5-HT)受体之一(即5-HT1B受体)的基因敲除小鼠,在攻击行为以及与阳性强化相关的行为背景下,探讨冲动性的概念及其与神经递质5-羟色胺的关系。这种基因敲除小鼠表现出更多的冲动性攻击行为,更快地习得可卡因自我给药行为,并且比相应的野生型对照饮用更多的酒精。我们发现,这些小鼠的冲动特征并非源于认知功能的改变:在一项涉及在小的即时奖励和大的延迟奖励之间进行选择的认知任务中,基因敲除小鼠表现出完整的选择和计时能力,并且对奖励量有良好的辨别能力。因此,这种小鼠可能会成为成瘾和运动冲动性的动物模型。

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