Date of Award

Spring 1-1-2014

Document Type


Degree Name

Master of Science (MS)


Integrative Physiology

First Advisor

Monika Fleshner

Second Advisor

Benjamin N. Greenwood

Third Advisor

Ryan K. Bachtell


The mesocorticolimbic reward pathway is implicated in the development and treatment of stress-related psychiatric disorders such as anxiety and depression. Exercise can reduce the incidence of stress-related disorders, but the contribution of exercise reward to exercise-induced stress resistance is unknown. We have previously reported that the anxiolytic and antidepressant-like effects of exercise are independent of exercise controllability; whereby both voluntary and forced wheel running protect rats against behavioral consequences of stress. Voluntary wheel running has previously been shown to be rewarding, however, whether rats find forced wheel running rewarding is unknown. The goal of the current studies was to test the novel hypothesis that both voluntary and forced wheel running are similarly rewarding. Young adult, male Fischer 344 rats allowed voluntary or forced wheel access found running rewarding as measured by conditioned placed preference (CPP). In addition, the rewarding effects of wheel running were examined neurobiologically. Utilizing double label fluorescence in situ hybridization (FISH), voluntary and forced running rats re-exposed to the side of the CPP chamber previously paired with wheel running displayed greater conditioned activation (c-fos) of dynorphin-expressing direct pathway striatal neurons and tyrosine hydroxylase (TH)-expressing lateral ventral tegmental area (VTA) neurons compared to rats re-exposed to the side of the CPP chamber previously paired with the lack of a running wheel. These results demonstrate that both voluntary and forced wheel running elicit c-fos activity in both classic mesocorticolimbic reward circuitry, as well as dorsal striatal direct pathway circuitry more recently implicated in reward processing. The activation of these particular neural circuits could be instrumental to the rewarding effects of exercise. Moreover, the implications of these data suggest that rewarding pathways may contribute to the mechanisms by which exercise increases stress resistance. Our findings warrant the need for greater investigation into central reward circuitry not only to seek novel pharmacological targets, but also to improve and tailor exercise interventions in the prevention and treatment of stress related psychiatric disorders.