Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway.
Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway.
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DOI：
10.1523/jneurosci.1525-08.2008
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发表时间：
2008-09-03
期刊：
影响因子：
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通讯作者：
Salamone JD
中科院分区：
文献类型：
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作者：
Mingote S;Font L;Farrar AM;Vontell R;Worden LT;Stopper CM;Port RG;Sink KS;Bunce JG;Chrobak JJ;Salamone JD
以目标为导向的行动对与工作相关的反应成本很敏感，伏隔核中的多巴胺被认为可以调节动机行为中的努力程度。伏隔核等富含多巴胺的纹状体区域也含有大量腺苷 A2A 受体，因此，研究了腺苷 A2A 受体激动剂 CGS 21680 [2-p-(2-羧乙基) 苯乙氨基-5'-N-乙基甲酰胺腺苷] 的行为和神经化学效应。伏隔核腺苷 A2A 受体的刺激会扰乱高工作要求的工具性任务（即附加比例要求的间隔杠杆按压计划）的表现，但对工作要求较低的任务几乎没有影响。免疫组织化学研究表明，投射到腹侧苍白球的伏隔神经元表现出腺苷 A2A 受体免疫反应性。此外，局部注射 CGS 21680 激活伏隔核 A2A 受体可增加腹侧苍白球的细胞外 GABA 水平。对侧伏核注射 CGS 21680 和腹侧苍白球注射 GABAA 激动剂蝇蕈醇（即“断开”方法）也会损害反应输出，表明这些结构是调节用力的常见神经回路的一部分。因此，伏隔腺苷 A2A 受体似乎通过调节腹侧纹状体苍白球通路的活性来调节行为激活和努力相关过程。对这些前脑系统与努力相关的功能的研究可能有助于更好地理解动机的病理特征，例如精神运动减慢、无力和抑郁症中的疲劳。
Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine A2A receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A2A receptor agonist CGS 21680 [2-p-(2-carboxyethyl) phenethylamino-5′-N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A2A receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens neurons that project to the ventral pallidum showed adenosine A2A receptors immunoreactivity. Moreover, activation of accumbens A2A receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral injections of CGS 21680 into the accumbens and the GABAA agonist muscimol into ventral pallidum (i.e., “disconnection” methods) also impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus, accumbens adenosine A2A receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression.