Conditioned stress prevents cue-primed cocaine reinstatement only in stress-responsive rats. (3rd July 2016)

• Record Type: Journal Article
• Authors: Hadad, Natalie A.; Wu, Lizhen; Hiller, Helmut; Krause, Eric G.; Schwendt, Marek; Knackstedt, Lori A.
• Is Part Of: Stress. Volume 19:Number 4(2016:Jul.)
• Page Start: 406
• Page End: 418
• Publication Date: 2016-07-03
• Subjects: Addiction -- corticosterone -- CRH -- FKBP5 -- Glcci1 -- PTSD; Stress (Physiology) -- Periodicals; 616.98
• DOI: 10.1080/10253890.2016.1189898
• Languages: English
• ISSNs: 1025-3890

Abstract

Abstract: Neurobiological mechanisms underlying comorbid posttraumatic stress disorder (PTSD) and cocaine use disorder (CUD) are unknown. We aimed to develop an animal model of PTSD + CUD to examine the neurobiology underlying cocaine-seeking in the presence of PTSD comorbidity. Rats were exposed to cat urine once for 10-minutes and tested for anxiety-like behaviors one week later. Subsequently, rats underwent long-access (LgA) cocaine self-administration and extinction training. Rats were re-exposed to the trauma context and then immediately tested for cue-primed reinstatement of cocaine-seeking. Plasma and brains were collected afterwards for corticosterone assays and real-time qPCR analysis. Urine-exposed (UE; n = 23) and controls not exposed to urine (Ctrl; n = 11) did not differ in elevated plus maze behavior, but UE rats displayed significantly reduced habituation of the acoustic startle response (ASR) relative to Ctrl rats. A median split of ASR habituation scores was used to classify stress-responsive rats. UE rats ( n = 10) self-administered more cocaine on Day 1 of LgA than control rats (Ctrl + Coc; n = 8). Re-exposure to the trauma context prevented cocaine reinstatement only in stress-responsive rats. Ctrl + Coc rats had lower plasma corticosterone concentrations than Ctrls, and decreased gene expression of corticotropin releasing hormone (CRH) and Glcci1 in the hippocampus. Rats that self-administered cocaine displayed greater CRH expression in the amygdala that was independent of urine exposure. While we did not find that cat urine exposure induced a PTSD-like phenotype in our rats, the present study underscores the need to separate stressed rats into cohorts based on anxiety-like behavior in order to study individual vulnerability to PTSD + CUD.