Not All Antidepressants Are Created Equal: Differential Effects of Monoamine Uptake Inhibitors on Effort-Related Choice Behavior.
Not All Antidepressants Are Created Equal: Differential Effects of Monoamine Uptake Inhibitors on Effort-Related Choice Behavior.
复制标题
并非所有抗抑郁药都是一样的：单胺摄取抑制剂对努力相关选择行为的不同影响。
DOI：
10.1038/npp.2015.188
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Salamone,JohnD
中科院分区：
文献类型：
--
作者：
Yohn,SamanthaE;Collins,SamanthaL;Contreras-Mora,HectorM;Errante,EmilyL;Rowland,MargaretA;Correa,Merce;Salamone,JohnD
动机行为的特点是行为激活和高工作产出。此外，患有抑郁症和其他疾病的人会表现出与努力相关的动机症状，例如无力、精神运动迟缓和疲劳。基于努力的决策是通过任务提供在导致高价值强化物的高努力选项与低努力/低奖励选项之间进行选择的任务来研究的，并且此类任务可用作动机症状的动物模型。在本研究中，研究了囊泡单胺转运 (VMAT-2) 抑制剂丁苯那嗪 (TBZ) 与努力相关的影响。 TBZ 会阻碍囊泡储存，还会在人类中产生抑郁症状。此外，TBZ 改变了大鼠基于努力的选择，使动物偏向于低努力的替代方案。目前的研究调查了急性施用各种单胺摄取抑制剂逆转 TBZ 作用的能力。儿茶酚胺摄取抑制剂和抗抑郁药安非他酮可以减弱 TBZ 的努力相关作用，而安非他酮的这种作用可以通过 D 1 或 D 2 家族拮抗作用逆转。选择性多巴胺摄取阻滞剂 GBR12909 也减弱了 TBZ 的努力相关效应。 5-HT 摄取抑制剂氟西汀和去甲肾上腺素摄取抑制剂地昔帕明未能逆转 TBZ 的作用，单独或与 TBZ 联合使用这些药物的较高剂量会导致进一步的行为障碍。这些结果表明，作用于多巴胺传递的药物在逆转 TBZ 与努力相关的影响方面相对有效，并且与增强多巴胺传递的药物可能有效治疗人类与努力相关的精神症状的假设一致。
Motivated behavior can be characterized by behavioral activation and high work output. Moreover, people with depression and other disorders show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Effort-based decision making is studied using tasks offering choices between high effort options leading to highly valued reinforcers vs low effort/low reward options, and such tasks could be useful as animal models of motivational symptoms. In the present studies the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine (TBZ) were investigated. TBZ blocks vesicular storage and also produces depressive symptoms in humans. Moreover, TBZ alters effort-based choice in rats, biasing animals toward low effort alternatives. The present studies investigated the ability of acute administration of various monoamine uptake inhibitors to reverse the effects of TBZ. Effort-related effects of TBZ were attenuated by the catecholamine uptake inhibitor and antidepressant bupropion, and this effect of bupropion was reversed by either D 1 or D 2 family antagonism. The effort-related effects of TBZ were also attenuated by the selective dopamine uptake blocker GBR12909. The 5-HT uptake inhibitor fluoxetine and the norepinephrine uptake inhibitor desipramine failed to reverse the effects of TBZ, and higher doses of these drugs, given alone or in combination with TBZ, led to further behavioral impairments. These results indicate that drugs acting on dopamine transmission are relatively effective at reversing the effort-related effects of TBZ, and are consistent with the hypothesis that drugs that enhance dopamine transmission may be effective at treating effort-related psychiatric symptoms in humans.