title: Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.
abstract: Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Eagle
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Robby
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kohler
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Friedman
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Chelsea P
authors.initials: CP
authors.lastname: Liebowitz
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA; Department of Anesthesiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Galloway
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Enman
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Jutkiewicz
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: sperrine@med.wayne.edu.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Perrine
mesh_terms: D017109:Akathisia, Drug-Induced / Q000503:physiopathology; D000818:Animals; D002408:Catheters, Indwelling; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D015331:Cohort Studies; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine
keywords: Animal model; Cocaine; Posttraumatic stress disorder; Self-administration; Sensitization; Single prolonged stress