Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine

- Predator odor stress results in distinct susceptible and resilient populations.
- Susceptible subjects show a sensitization of the dopaminergic response to cocaine.
- Susceptible subjects express increases in the motivation to self-administer cocaine.
- Active and passive resilience mechanisms may normalize cocaine effects and behavior.

Patients with post-traumatic stress disorder have a heightened vulnerability to developing substance use disorders; however, the biological underpinnings of this vulnerability remain unresolved. We used the predator odor stress model of post-traumatic stress disorder with segregation of subjects as susceptible or resilient based on elevated plus maze behavior and context avoidance. We then determined behavioral and neurochemical differences across susceptible, resilient, and control populations using a panel of behavioral and neurochemical assays. Susceptible subjects showed a significant increase in the motoric and dopaminergic effects of cocaine, and this corresponded with heightened motivation to self-administer cocaine. Resilient subjects did not show differences in the motoric effects of cocaine, in dopamine signaling in vivo, or in any measure of cocaine self-administration. Nonetheless, we found that these animals displayed elevations in both the dopamine release-promoting effects of cocaine and dopamine autoreceptor sensitivity ex vivo. 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.