title: Anhedonia, Reduced Cocaine Reward, and Dopamine Dysfunction in a Rat Model of Posttraumatic Stress Disorder.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) co-occurs with substance use disorders at high rates, but the neurobiological basis of this relationship is largely unknown. PTSD and drug addiction each involve dysregulation of brain reward circuitry; therefore, the identification of pathology of the mesolimbic dopamine system may aid in understanding their functional relationship. Dopamine reward dysfunction also may be relevant to the mechanisms underlying the PTSD symptoms of anhedonia and emotional numbing.
  
  
  METHODS
  Single-prolonged stress (SPS) was used as a rat model of PTSD, and a series of behavioral and neuropharmacologic assays were applied to assess the impact of SPS on reward, cocaine intake, and components of the striatal dopamine system.
  
  
  RESULTS
  Exposure to SPS increased anhedonia-like behaviors and decreased the rewarding properties of cocaine compared with control handling. Altered cocaine intake during extended access self-administration sessions was observed in rats exposed to SPS, further suggesting a difference in the reinforcing properties of cocaine following severe stress. SPS reduced tissue content of dopamine and its metabolites in the striatum, as well as altered striatal dopamine transporter and D2, but not D1, receptor densities.
  
  
  CONCLUSIONS
  These results support a role for altered dopaminergic transmission in reduced reward function in PTSD. Pathology of the dopamine system and the degradation of reward processes may contribute to PTSD symptomology and have implications for co-occurring psychiatric disorders such as substance abuse or depression.
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania; Center for Substance Abuse Research (NME, EMU), Temple University School of Medicine, Philadelphia, Pennsylvania. Electronic address: nicole.enman@temple.edu.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Enman
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Kayti
authors.initials: K
authors.lastname: Arthur
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Ward
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences (SAP), Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Perrine
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania; Center for Substance Abuse Research (NME, EMU), Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Unterwald
mesh_terms: D059445:Anhedonia / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D008297:Male; D017072:Neostriatum / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012201:Reward; D012646:Self Administration; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003042:Cocaine; D004298:Dopamine
keywords: Cocaine; Dopamine; PTSD; Posttraumatic stress disorder; Reward; Self-administration