Date of Award
Fall 12-3-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biological Sciences
First Advisor
Robert Wheeler
Second Advisor
Jennifer Evans
Third Advisor
John Mantsch
Abstract
We all experience adversity in our lives, and we must be able to effectively respond to these challenges in order to thrive. One way to respond to stressors is to change one’s behavior to cope with the stress. This can include escaping or avoiding the stressor, focusing effort to diminish the effect of the stressor, or other coping strategies such as drug use. In fact, stress is one of the principal triggers of relapse for those in the abstinence phase of a substance use disorder and it exacerbates a variety of other disorders. Therefore, it is critical to understand the way the brain encodes these aversive stimuli and how it then motivates us to respond to the stressor. Extensive literature connects such motivated behaviors with dopamine function in the brain. Given that stress has been reported to alter motivated behavior in both adaptive and maladaptive ways, and that it changes dopamine signaling, it is essential to understand how the brain uses dopamine to encode negative events, how this changes behavior, and how those may vary between acute and chronic stressors. In this dissertation, I describe several studies that contribute to our understanding of how aversive stimuli alter dopamine and behavior. I first replicate the finding that aversive stimuli increase cocaine self-administration. I then use fiber photometry to show that the same stimulus reduces dopamine in a key reward region, the nucleus accumbens (NAc), and that this reduction is correlated with increased cocaine self-administration. Next, I demonstrate that this aversion-induced reduction in dopamine is also correlated with an increase in an adaptive behavior, escape from the aversive stimulus itself. I then extend this finding by testing whether prior experience to chronic stress changes dopaminergic signaling or escape behavior, showing that chronic stress invigorates escape behavior and alters baseline dopamine release. Finally, I provide pharmacological evidence that the aversion-induced reductions in NAc dopamine are partially regulated via the activation of GABAB receptors in the ventral tegmental area. These data provide additional information about the ways the brain responds to naturally occurring adversity, thereby moving us closer to effective interventions for stress-related disorders.
Comments
Doctor of Philosophy (PhD)