Bupropion increases selection of high effort activity in rats tested on a progressive ratio/chow feeding choice procedure: implications for treatment of effort-related motivational symptoms.
Bupropion increases selection of high effort activity in rats tested on a progressive ratio/chow feeding choice procedure: implications for treatment of effort-related motivational symptoms.
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安非他酮增加了对渐进比例/食物喂养选择程序测试的大鼠的高努力活动的选择：对治疗与努力相关的动机症状的影响。
DOI：
10.1093/ijnp/pyu017
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Salamone,JohnD
中科院分区：
文献类型：
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作者：
Randall,PatrickA;Lee,ChristieA;Podurgiel,SamanthaJ;Hart,Evan;Yohn,SamanthaE;Jones,Myles;Rowland,Margaret;López-Cruz,Laura;Correa,Mercè;Salamone,JohnD
背景抑郁症及其相关障碍的特征是行为激活、努力和其他心理/动机功能障碍的缺陷。抑郁症患者表现出与努力相关的决策的改变，并偏向于选择低努力的活动。有人建议，努力相关的决策的动物试验可能是有用的，作为精神病理学中看到的动机功能障碍的模型。MethodsBecause临床研究表明，抑制儿茶酚胺摄取可能是治疗努力相关的动机症状的有用策略，本研究评估了安非他酮增加大鼠对努力相关的决策测试作出反应的工作输出的能力（即，渐进比率/食物喂养选择任务）。有了这个任务，大鼠可以选择工作之间的一个首选的食物（高碳水化合物颗粒）通过杠杆按下一个渐进的比例时间表与获得一个不太喜欢的实验室的食物，是免费提供的chamber.ResultsBupropion（10.0-40.0毫克/公斤腹腔内）显着增加了所有措施的渐进比例杠杆按压，但减少了食物的摄入量。这些影响在渐进比率计划中具有低基线水平的工作输出的动物中最大。由于多巴胺参与与努力相关的过程，因此检查了安非他酮对多巴胺传递标志物的影响。安非他酮通过微透析测定升高了多巴胺核心细胞外多巴胺水平，并增加了磷酸化多巴胺和环AMP相关磷蛋白32 kDaltons（pDARPP-32）免疫反应性的方式与D1和D2受体stimulation.ConclusionThe能力的安非他酮，以增加努力的工具行为可能有影响的病理生理学和治疗的努力-相关的动机症状
BackgroundDepression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology.MethodsBecause clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber.ResultsBupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation.ConclusionThe ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans.