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

NEUROPHARMACOLOGY

卷:125

Article

Brodnik, Zachary D.¹  Black, Emily M.¹  Clark, Meagan J.¹  Kornsey, Kristen N.¹  Snyder, Nathaniel W.²  Espana, Rodrigo A.¹ 

[1] Drexel Univ, Dept Neurobiol & Anat, Coll Med, 2900 W Queen Lane, Philadelphia, PA 19129 USA

[2] Drexel Univ, AJ Drexel Autism Inst, 3141 Chestnut St, Philadelphia, PA 19104 USA

关键词: PTSD;    DAT;    Dopamine;    Resilient;    Susceptible;    Voltammetry;   

DOI  :  10.1016/j.neuropharm.2017.07.032

来源: Elsevier

【 摘 要 】

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 selfadminister 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. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

Free