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在有针对性地缺失AMPA受体谷氨酸受体1亚基的小鼠中,工具性反应的特定结果贬值受损。

Impaired outcome-specific devaluation of instrumental responding in mice with a targeted deletion of the AMPA receptor glutamate receptor 1 subunit.

作者信息

Johnson Alexander W, Bannerman David M, Rawlins Nicholas P, Sprengel Rolf, Good Mark A

机构信息

School of Psychology, Cardiff University, Cardiff CF10 3YG, United Kingdom.

出版信息

J Neurosci. 2005 Mar 2;25(9):2359-65. doi: 10.1523/JNEUROSCI.4146-04.2005.

Abstract

The present study evaluated the proposal that mice with a targeted deletion of the glutamate receptor 1 (GluR1) subunit of the AMPA receptor are impaired in using an instrumental or pavlovian signal to gain access to a representation of the sensory-specific motivational properties of a primary reward. In experiment 1, mice were trained to approach two goal boxes in a plus-maze; each goal box contained a different reward (sucrose solution vs food pellet). After acquisition, one of the rewards was devalued by an outcome-specific satiety procedure. Subsequent test trials performed in extinction showed an increase in the latency to enter the devalued goal arm, relative to the nondevalued goal arm in control but not GluR1-/- mice. In experiment 2, a similar outcome-specific satiety procedure was used to examine the effects of reward devaluation on an instrumental nose-poke response. During testing, control but not GluR1-/- mice decreased their rate of responding on a nose poke associated with a devalued reward. A subsequent choice test showed that GluR1-/- mice were able to discriminate between the devalued and nondevalued outcomes used in both experiments. These deficits mirror those seen after lesions of the basolateral amygdala and suggests that GluR1-mediated neurotransmission in this region contributes to encoding the relationship between sensory-specific aspects of reward and their incentive value.

摘要

本研究评估了以下假设

靶向缺失α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体的谷氨酸受体1(GluR1)亚基的小鼠,在利用工具性或巴甫洛夫信号获取初级奖赏的感觉特异性动机属性表征方面存在缺陷。在实验1中,训练小鼠在十字迷宫中接近两个目标箱;每个目标箱包含不同的奖赏(蔗糖溶液与食物颗粒)。习得后,通过特定结果的饱腹感程序使其中一种奖赏贬值。在消退期进行的后续测试试验表明,相对于对照组但不是GluR1基因敲除小鼠的未贬值目标臂,进入贬值目标臂的潜伏期增加。在实验2中,使用类似的特定结果饱腹感程序来检查奖赏贬值对工具性鼻触反应的影响。在测试期间,对照组但不是GluR1基因敲除小鼠降低了与贬值奖赏相关的鼻触反应率。随后的选择测试表明,GluR1基因敲除小鼠能够区分两个实验中使用的贬值和未贬值结果。这些缺陷与基底外侧杏仁核损伤后观察到的缺陷相似,表明该区域中GluR1介导的神经传递有助于编码奖赏的感觉特异性方面与其激励价值之间的关系。

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