Validation of a non-food or water motivated effort-based foraging task as a measure of motivational state in male mice

Abstract

Disorders of motivation such as apathy syndrome are highly prevalent across neurological disorders but do not yet have an agreed treatment approach. The use of translational behavioural models can provide a route through which to meaningfully screen novel drug targets. Methods that utilise food deprivation in contrived environments may lack the sensitivity to detect deficits in self-initiated behaviour, and may have limited translation to normal behaviour. Animals monitored in more naturalistic environments may display more ethologically-relevant behaviours of greater translational value. Here, we aimed to validate a novel, non-food or water motivated effort-based foraging task as a measure of motivational state in mice. In this task, the mouse can freely choose to exert effort to forage nesting material and shuttle it back to a safe and enclosed environment. The amount of nesting material foraged is used as a readout of motivational state. Acute dopaminergic modulation with haloperidol, amphetamine and methylphenidate, and two phenotypic models known to induce motivational deficits (healthy ageing and chronic administration of corticosterone) were used to validate this task. Consistent with other effort-based decision-making tasks we find that foraging behaviour is sensitive to acute modulation of dopaminergic transmission. We find that both phenotypic models induce differing deficits in various aspects of foraging behaviour suggesting that the task may be used to parse different behavioural profiles from distinct disease phenotypes. Thus, without requiring extended training periods or physiological deprivation, this task may represent a refined and translational preclinical measure of motivation.