Neuroscience Graduate Program, Rutgers University, Piscataway, USA.
Department of Psychology, Behavioral and Systems Neuroscience, Rutgers University, 152 Frelinghuysen Rd., Piscataway, NJ, 08854, USA.
Psychopharmacology (Berl). 2020 Jul;237(7):2103-2110. doi: 10.1007/s00213-020-05521-z. Epub 2020 Apr 18.
Effort-related choice tasks are used to study aspects of motivation in both rodents and humans (Der-Avakian and Pizzagalli Biol Psychiatry 83(11):932-939, 2018). Various dopaminergic manipulations and antidepressant treatments can shift responding to these tasks (Randall et al. Int J Neuropsychopharmacol 18(2), 2014; Yohn et al. Psychopharmacology 232(7):1313-1323, 2015). However, while chronic stress can precipitate mood disorders in humans, there is relatively little known about whether chronic stress elicits maladaptive behaviors in rodent effort-related choice tasks.
Chronic corticosterone (CORT) elicits an increase in negative maladaptive behaviors in male mice (David et al. Neuron 62(4):479-493, 2009; Gourley et al. Biol Psychiatry 64(10):884-890, 2008; Olausson et al. Psychopharmacology 225(3):569-577, 2013). We hypothesized that chronic CORT administration to male mice would reduce motivation for a higher effort, higher reward option, and shift responding to a less effortful, but a lesser reward.
Adult male C57BL/6J mice were administered either vehicle (n = 10) or CORT (n = 10) (~ 9.5 mg/kg/day) in their drinking water for 4 weeks, and then throughout all behavioral experiments (15 weeks total), and were tested in a Y-Maze barrier task and a fixed ratio concurrent (FR/chow) choice task.
Chronic CORT reduced Y-maze HR arm choice when more effort was required to obtain the 4 food pellets (15-cm barrier in the high-reward (HR) arm, p < 0.001; 20-cm barrier in HR arm, p < 0.001) and shifted choice to the low reward (LR) arm where only 2 pellets were available. Chronic CORT also reduced lever pressing for food pellets in FR30/chow sessions of the concurrent choice task (p = 0.009), without impacting lab chow consumed.
Chronic stress induces maladaptive shifts in effort-related choice behavior in the Y-maze barrier task in male mice. Furthermore, males subjected to chronic CORT administration show reduced lever pressing in FR30/chow sessions where lab chow is concurrently available. These data demonstrate that chronic corticosterone reduces motivation to work for and obtain a highly rewarding reinforcer when a lesser reinforcer is concurrently available.
努力相关的选择任务被用于研究啮齿动物和人类的动机的各个方面(Der-Avakian 和 Pizzagalli Biol Psychiatry 83(11):932-939, 2018)。各种多巴胺能的操作和抗抑郁治疗可以改变对这些任务的反应(Randall 等人。Int J Neuropsychopharmacol 18(2), 2014; Yohn 等人。Psychopharmacology 232(7):1313-1323, 2015)。然而,虽然慢性应激可以引发人类的情绪障碍,但对于慢性应激是否会引起啮齿动物努力相关选择任务中的不良适应行为,我们知之甚少。
慢性皮质酮(CORT)会增加雄性小鼠的消极适应不良行为(David 等人。Neuron 62(4):479-493, 2009; Gourley 等人。Biol Psychiatry 64(10):884-890, 2008; Olausson 等人。Psychopharmacology 225(3):569-577, 2013)。我们假设,慢性 CORT 给药会降低雄性小鼠对更高努力、更高奖励选择的动机,并促使他们选择更省力但奖励更少的选项。
成年雄性 C57BL/6J 小鼠被给予载体(n = 10)或 CORT(n = 10)(约 9.5 mg/kg/天)在他们的饮用水中,持续 4 周,然后在所有行为实验中(总共 15 周),并在 Y 型迷宫障碍任务和固定比率并发(FR/chow)选择任务中进行测试。
慢性 CORT 降低了需要更多努力才能获得 4 个食物球的 Y 型迷宫 HR 臂选择(15-cm 障碍物在 HR 臂中,p < 0.001;20-cm 障碍物在 HR 臂中,p < 0.001),并将选择转移到仅提供 2 个球的低奖励(LR)臂。慢性 CORT 还降低了 FR30/chow 并发选择任务中食物球的按压杆次数(p = 0.009),而不影响实验室消耗的食物。
慢性应激导致雄性小鼠在 Y 型迷宫障碍任务中出现与努力相关的选择行为的不良适应。此外,接受慢性 CORT 给药的雄性动物在 FR30/chow 同时提供实验室食物的情况下,按压杆的次数减少。这些数据表明,慢性皮质酮降低了雄性小鼠对高度奖励强化物的工作和获得动机,而当提供较少的强化物时。