title: Impaired Ethanol-Induced Sensitization and Decreased Cannabinoid Receptor-1 in a Model of Posttraumatic Stress Disorder.
abstract: Impaired striatal neuroplasticity may underlie increased alcoholism documented in those with posttraumatic stress disorder (PTSD). Cannabinoid receptor-1 (CB1) is sensitive to the effects of ethanol (EtOH) and traumatic stress, and is a critical regulator of striatal plasticity. To investigate CB1 involvement in the PTSD-alcohol interaction, this study measured the effects of traumatic stress using a model of PTSD, mouse single-prolonged stress (mSPS), on EtOH-induced locomotor sensitization and striatal CB1 levels.
  
  
  
  Mice were exposed to mSPS, which includes: 2-h restraint, 10-min group forced swim, 15-min exposure to rat bedding odor, and diethyl ether exposure until unconsciousness or control conditions. Seven days following mSPS exposure, the locomotor sensitizing effects of EtOH were assessed. CB1, post-synaptic density-95 (PSD95), and dopamine-2 receptor (D2) protein levels were then quantified in the dorsal striatum using standard immunoblotting techniques.
  
  
  
  Mice exposed to mSPS-EtOH demonstrated impaired EtOH-induced locomotor sensitization compared to Control-EtOH mice, which was accompanied by reduced striatal CB1 levels. EtOH increased striatal PSD95 in control and mSPS-exposed mice. Additionally, mSPS-Saline exposure increased striatal PSD95 and decreased D2 protein expression, with mSPS-EtOH exposure alleviating these changes.
  
  
  
  These data indicate that the mSPS model of PTSD blunts the behavioral sensitizing effects of EtOH, a response that suggests impaired striatal neuroplasticity. Additionally, this study demonstrates that mice exposed to mSPS and repeated EtOH exposure decreases CB1 in the striatum, providing a mechanism of interest for understanding the effects of EtOH following severe, multimodal stress exposure.
authors.affiliation: Research Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America.|Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Matchynski-Franks
authors.affiliation: Research Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America.|Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Susick
authors.affiliation: Research Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America.|Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Brandy L
authors.initials: BL
authors.lastname: Schneider
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Perrine
authors.affiliation: Research Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America.|Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Alana C
authors.initials: AC
authors.lastname: Conti
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D051528:Guanylate Kinases / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D043884:Receptor, Cannabinoid, CB1; D017448:Receptors, Dopamine D2; D000431:Ethanol; D051528:Guanylate Kinases