Basic mechanisms and translational approaches to understanding effort-based choice

Effort is a cost that must be overcome to procure rewards, and organisms frequently make cost benefit decisions based on effort in choosing which options to pursue. The majority of previous work probing the neural mechanisms of effort-based choice has focused on the striatum and dopaminergic signaling therein, and less work has investigated behavioral or environmental factors that contribute. In all of the following experiments, an effort-based choice task was adopted from previous findings where rats could freely choose between a high effort, preferred option and a low effort, less preferred option. The high effort option was lever progressing on a progressive ratio schedule for sucrose pellets in which each successive reward became more difficult to earn. The low effort option was freely available lab chow concurrently available that had no work requirement, but was less palatable. Thus, rats could freely choose between these options and self- titrate the amount of effort they were willing to exert. A number of control tasks were used to control for changes in motoric ability, appetite, or food preference. By omitting the freely available lab chow and testing subjects for progressive ratio performance, any impairment in motoric ability, memory, and general willingness to exert effort, rather than cost-benefit valuation per se, could be ruled out. To test whether manipulations had effects on appetite or food preference, rats were tested with both food options freely concurrently available where they did not have to work for either. In the case of manipulations that took place prior to behavioral testing, we recorded the number of sessions it took to reach stable performance to rule out impairments in learning.In the second chapter of this dissertation, the basolateral amygdala (BLA) was tested for its effects in effort-based choice. In a series of experiments, we found that BLA pharmacological inactivations reduced high effort lever pressing specifically in the context of choice, without impairing progressive ration responding when it was the only option. These effects were also not due to changes in appetite or food preference. Chapter three details effects of anterior cingulate cortex (ACC) lesions. Much like BLA inactivations, lesions of ACC decreased choice lever pressing without affecting lever pressing ability, appetite, or food preference. In chapter four, we tested whether a behavioral manipulation, withdrawal from methamphetamine self-administration, had effects on effort based choice. Methamphetamine withdrawn animals exhibited decreased choice lever pressing, which was not due to general work aversion, learning impairments, changes in appetite, or changes in food preference. This decreased effort was accompanied by decreased activation of anterior cingulate, ventral striatum, and amygdala. In the last set of experiments, we replicated results from the ACC lesion experiments using a modern chemogenetic approach. Finally, all of the above findings are discussed with their relevance to future studies and broader implications of the basic science of effort