Behavioral Neuroscience Division, Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269-1020, USA.
Behavioral Neuroscience Division, Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269-1020, USA; Area de Psicobiologia, Universitat Jaume I, Castelló, Spain.
Pharmacol Biochem Behav. 2021 Mar;202:173115. doi: 10.1016/j.pbb.2021.173115. Epub 2021 Jan 23.
Selective serotonin transport (SERT) inhibitors such as fluoxetine are the most commonly prescribed treatments for depression. Although efficacious for many symptoms of depression, motivational impairments such as psychomotor retardation, anergia, fatigue and amotivation are relatively resistant to treatment with SERT inhibitors, and these drugs have been reported to exacerbate motivational deficits in some people. In order to study motivational dysfunctions in animal models, procedures have been developed to measure effort-related decision making, which offer animals a choice between high effort actions leading to highly valued reinforcers, or low effort/low reward options. In the present studies, male and female rats were tested on two different tests of effort-based choice: a fixed ratio 5 (FR5)/chow feeding choice procedure and a running wheel (RW)/chow feeding choice task. The baseline pattern of choice differed across tasks for males and females, with males pressing the lever more than females on the operant task, and females running more than males on the RW task. Administration of the SERT inhibitor and antidepressant fluoxetine suppressed the higher effort activity on each task (lever pressing and wheel running) in both males and females. The serotonin receptor mediating the suppressive effects of fluoxetine is uncertain, because serotonin antagonists with different patterns of receptor selectivity failed to reverse the effects of fluoxetine. Nevertheless, these studies uncovered important sex differences, and demonstrated that the suppressive effects of fluoxetine on high effort activities are not limited to tasks involving food reinforced behavior or appetite suppressive effects. It is possible that this line of research will contribute to an understanding of the neurochemical factors regulating selection of voluntary physical activity vs. sedentary behaviors, which could be relevant for understanding the role of physical activity in psychiatric disorders.
选择性 5-羟色胺再摄取抑制剂（SSRIs），如氟西汀，是治疗抑郁症最常用的药物。尽管 SSRIs 对抑郁症的许多症状都有效，但动机障碍，如运动迟滞、无力、疲劳和动力缺乏，对 SSRIs 的治疗相对具有抗性，并且据报道，这些药物会使一些人恶化动机缺陷。为了在动物模型中研究动机功能障碍，已经开发了测量与努力相关的决策制定的程序，这些程序为动物提供了在高努力行为与高价值强化物之间进行选择的机会，或者在低努力/低奖励选项之间进行选择。在本研究中，雄性和雌性大鼠分别在两种不同的基于努力的选择测试中进行了测试：固定比率 5（FR5）/ 食物选择程序和跑步轮（RW）/ 食物选择任务。基线选择模式因任务而异，雄性在操作性任务中按压杠杆的次数多于雌性，而雌性在 RW 任务中跑步的次数多于雄性。选择性 5-羟色胺再摄取抑制剂和抗抑郁药氟西汀的给药抑制了雄性和雌性在每项任务（按压杠杆和跑步）中的更高努力活动。介导氟西汀抑制作用的血清素受体尚不确定，因为具有不同受体选择性模式的血清素拮抗剂未能逆转氟西汀的作用。尽管如此，这些研究揭示了重要的性别差异，并证明氟西汀对高努力活动的抑制作用不仅限于涉及食物强化行为或食欲抑制作用的任务。有可能，这一系列研究将有助于理解调节自愿体力活动与久坐行为选择的神经化学因素，这可能与理解体力活动在精神疾病中的作用有关。
