title: Conditioned stress prevents cue-primed cocaine reinstatement only in stress-responsive rats.
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.
authors.affiliation: a Department of Psychology , University of Florida , Gainesville , FL , USA ;
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Hadad
authors.affiliation: a Department of Psychology , University of Florida , Gainesville , FL , USA ;
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wu
authors.affiliation: b Department of Pharmacodynamics , University of Florida , Gainesville , FL , USA.
authors.forename: Helmut
authors.initials: H
authors.lastname: Hiller
authors.affiliation: b Department of Pharmacodynamics , University of Florida , Gainesville , FL , USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Krause
authors.affiliation: a Department of Psychology , University of Florida , Gainesville , FL , USA ;
authors.forename: Marek
authors.initials: M
authors.lastname: Schwendt
authors.affiliation: a Department of Psychology , University of Florida , Gainesville , FL , USA ;
authors.forename: Lori A
authors.initials: LA
authors.lastname: Knackstedt
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D003463:Cues; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D012646:Self Administration; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D018765:Dopamine Uptake Inhibitors; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine; D003345:Corticosterone
keywords: Addiction; CRH; FKBP5; Glcci1; PTSD; corticosterone