Chronic corticosterone shifts effort-related choice behavior in male mice.

ABSTRACT

RATIONALE 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.