| Summary: | Amotivational states and insufficient recruitment of mental effort have been observed in a variety of clinical populations, including depression, traumatic brain injury, post-traumatic stress disorder, and attention-deficit/hyperactivity disorder. Previous animal models of effort-based decision making have utilized physical costs whereas human studies of effort have been primarily cognitive in nature, and it is unclear whether the two types of effortful decision making are underpinned by the same neurobiological processes. We therefore validated a novel rat Cognitive Effort Task (rCET) based on the five-choice serial reaction-time task, a well-established measure of attention and impulsivity. Within each rCET trial, rats were given the choice between an easy or hard visuospatial discrimination, and successful hard trials were rewarded with double the number of sugar pellets. Similar to previous human studies, stable individual variation in choice behaviour was observed, with “workers” choosing hard trials significantly more than their “slacker” counterparts. We used a variety of pharmacological agents as well as temporary inactivation of select brain regions, and showed that the effects of these manipulations often interacted with animals’ baseline preferences. Amphetamine and caffeine caused workers to “slack off”, whereas slackers “worked harder” under amphetamine but not caffeine. Dopamine antagonism had no discernible effects on animals’ choice, contrary to the physical-effort literature. The cholinergic drug nicotine decreased slackers’ willingness to expend effort, whereas scopolamine more substantially decreased workers’ choice of the high-effort option. Temporary inactivation of the basolateral amygdala caused workers to slack off and slackers to work harder, whereas anterior cingulate and medial prefrontal cortex inactivations caused all animals to slack off. In sum, we have shown for the first time that rats are differentially sensitive to cognitive effort when making decisions, independent of other processes such as impulsivity, and these baseline differences appear to be reflected by differences in underlying neurobiology. Further, we demonstrate that mental and physical effort are in part dissociable, both behaviourally and in terms of neurochemistry and neural circuitry. Such findings could inform our understanding of the neurobiological basis of decision making as well as impairments in effort-based decision making, and may contribute to novel therapeutic interventions. === Medicine, Faculty of === Graduate
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