NUCLEUS ACCUMBENS AND EFFORT-RELATED FUNCTIONS: BEHAVIORAL AND NEURAL MARKERS OF THE INTERACTIONS BETWEEN ADENOSINE A2A AND DOPAMINE D2 RECEPTORS
NUCLEUS ACCUMBENS AND EFFORT-RELATED FUNCTIONS: BEHAVIORAL AND NEURAL MARKERS OF THE INTERACTIONS BETWEEN ADENOSINE A2A AND DOPAMINE D2 RECEPTORS
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DOI：
10.1016/j.neuroscience.2009.12.056
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发表时间：
2010-04-14
期刊：
影响因子：
3.3
通讯作者：
Salamone, J. D.
中科院分区：
文献类型：
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作者：
Farrar, A. M.;Segovia, K. N.;Salamone, J. D.
伏隔核多巴胺(DA)是调节强化寻求行为和努力相关选择行为的工作输出的大脑回路的重要组成部分。此外，有证据表明DA D-2和腺苷A(2A)受体功能之间存在相互作用。全身应用腺苷A(2A)拮抗剂可逆转D-2拮抗剂在评估努力相关选择的任务中的作用。本实验旨在确定伏隔核是否是腺苷A(2A)和多巴胺D-2拮抗剂相互作用调节努力相关选择行为的大脑区域。同时使用固定比例5(FR5)/食物喂养程序；通过该程序，大鼠可以选择完成FR5杠杆按压要求的首选食物(即高碳水化合物可操作颗粒)或接近并食用免费可获得的食物(即标准啮齿动物食物)。经过这一程序训练的大鼠大部分时间都在按下杠杆，以获得首选的食物，而同时获得的食物中吃得很少。脑室注射选择性多巴胺D-2受体拮抗剂乙氯必利(1.0、2.0、4.0 mU g)至伏核核心，但不向背侧对照部位注射，可抑制FR5水平的压低，并增加对自由食物的摄取。无论是全身注射还是伏隔体内注射腺苷A(2A)受体拮抗剂MSX-3，都能逆转依替氯必利对努力相关选择的影响。伏隔核内注射依替氯必利也增加了c-Fos免疫反应性的局部表达，这种作用可被MSX-3联合应用而减弱。腺苷和多巴胺系统相互作用，调节工具行为和努力相关的过程，而伏隔核是这种相互作用的重要部位。这些发现可能会对精神症状的治疗有所启示，如精神运动减慢、神经痛和疲劳。(C)2010年IBRO。爱思唯尔有限公司出版。保留所有权利。
Nucleus accumbens dopamine (DA) is a critical component of the brain circuitry regulating work output in reinforcement-seeking behavior and effort-related choice behavior. Moreover, there is evidence of an interaction between DA D-2 and adenosine A(2A) receptor function. Systemic administration of adenosine A(2A) antagonists reverses the effects of D-2 antagonists on tasks that assess effort related choice. The present experiments were conducted to determine if nucleus accumbens is a brain locus at which adenosine A(2A) and DA D-2 antagonists interact to regulate effort-related choice behavior. A concurrent fixed ratio 5 (FR5)/chow feeding procedure was used; with this procedure, rats can choose between completing an FR5 lever-pressing requirement for a preferred food (i.e., high carbohydrate operant pellets) or approaching and consuming a freely available food (i.e., standard rodent chow). Rats trained with this procedure spend most of their time pressing the lever for the preferred food, and eat very little of the concurrently available chow. Intracranial injections of the selective DA D-2 receptor antagonist eticlopride (1.0, 2.0, 4.0 mu g) into nucleus accumbens core, but not a dorsal control site, suppressed FR5 lever-pressing and increased consumption of freely available chow. Either systemic or intra-accumbens injections of the adenosine A(2A) receptor antagonist MSX-3 reversed these effects of eticlopride on effort-related choice. Intra-accumbens injections of eticlopride also increased local expression of c-Fos immunoreactivity, and this effect was attenuated by co-administration of MSX-3. Adenosine and DA systems interact to regulate instrumental behavior and effort-related processes, and nucleus accumbens is an important locus for this interaction. These findings may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, anergia and fatigue. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.