Pharmacological characterisation of the effort for reward task as a measure of motivation for reward in male mice

Abstract

Rationale Motivational deficits are a common symptom shared across multiple psychiatric and neurodegenerative disorders. Effort-based decision-making tasks are a translatable method for assessing motivational state. Much of the preclinical validation of the task derives from acute pharmacological manipulations in rats. However, mice currently offer a greater genetic toolkit to study risk genes and phenotypic models. Despite this, there is limited characterisation of their behaviour in this type of motivation task. Objectives Here, we investigate the effort for reward (EfR) task as a measure of motivational state in mice using drugs previously shown to modulate effort-based decision-making in rats and humans. Method Using male C57bl/6j mice, we test the effects of drugs which modulate DA transmission. We also test the effects of CP101-606 which does not act directly via DA modulation but has been shown to exert beneficial effects on motivational state. Finally, we test the sensitivity of the task to a chronic corticosterone (CORT) treatment. Results Amphetamine, methylphenidate, and CP101606 in mice increased high-effort responses for high-value reward, while administration of haloperidol decreased high-effort responses. Surprisingly, tetrabenazine had no effect at the doses tested. Chronic, low-dose CORT consumption did not alter task performance. Conclusion These data suggest that the EfR task is sensitive to acute dopaminergic modulation and NR2B selective antagonism in mice. However, it may lack sensitivity to non-acute phenotypic models. Further work is required to demonstrate the utility of the task in this context.

Characterisation of behaviours relevant to apathy syndrome in the aged male rat

“…Where a p value of <0.1 was found it was reported in the results as a trend level effect but not further analysed. A priori and consistent with other work (Marangoni et al, 2023), statistical outliers were defined as data points 2 standard deviations from the group mean. Where this occurred, these points were excluded, and replaced with the group mean to allow repeated measures analysis where required.…”