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Trauma induced alterations in mesolimbic dopamine system activity and cocaine use vulnerability
Dissertation   Open access

Trauma induced alterations in mesolimbic dopamine system activity and cocaine use vulnerability

Zachary David Brodnik
Doctor of Philosophy (Ph.D.), Drexel University
Oct 2018
DOI:
https://doi.org/10.17918/qm92-f344
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Abstract

Neurosciences Post-traumatic stress disorder Stress (Psychology) Voltammetry Cocaine Dopamine Pharmacology
Patients with post-traumatic stress disorder (PTSD) have a heightened vulnerability to developing substance use disorders; however, the biological underpinnings of this vulnerability remain unresolved. We characterized and validated a version of the predator odor stress model of PTSD using segregation of subjects as susceptible or resilient based on avoidance and anxiety-like behavior. We then used a battery of in vivo and in vitro methods for examining differences in mesolimbic DA neurochemistry across control, resilient, and susceptible subjects. We found that susceptible subjects display a hyperdopaminergic phenotype, and that the dopaminergic effects of cocaine were elevated in vivo. We also found susceptible subject express increases in terminal cocaine sensitivity in vitro. Interestingly, while resilient subjects do not display any alterations in dopamine signaling in vivo, they do express elevations in both the dopamine release-promoting effects of cocaine and dopamine autoreceptor sensitivity in vitro. Additionally, we used cocaine self-administration to test several aspects of operant cocaine taking behaviors. Here we found that susceptible subjects show increases in the rate of cocaine self-administration acquisition and motivation to obtain cocaine while concomitantly expressing reductions in cocaine self-administration under low effort conditions. Resilient subjects did not differ from controls across any indices of cocaine self-administration. Overall, our results suggest that the experience of traumatic stress may produce alterations in dopamine systems that drive elevations in cocaine self-administration behavior in susceptible subjects, but may also produce both active and passive forms of resilience that function to prevent gross changes in cocaine's reinforcing efficacy in resilient subjects.

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