title: Valproic acid effects in the hippocampus and prefrontal cortex in an animal model of post-traumatic stress disorder.
abstract: Reactive oxygen species (ROS) and pro-inflammatory cytokines (PIC) are upregulated in post-traumatic stress disorder (PTSD). Histone deacetylase inhibitors (HDACi) modify genetic transcription and can diminish ROS and PIC escalation. They can also modulate levels of neurotransmitters such as catecholamines and serotonin (5-HT). Thus, this study sought to analyze the effects of the HDACi valproic acid (VA) on oxidative stress, inflammation, and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. PTSD-like effects were induced in male Sprague-Dawley rats (n=6/group×4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1h on days 1, 11, and 40 of a 40-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, the treatment group (PTSD+VA) and control group (Control+VA) rats were given VA in their drinking water for 30 days. The rats were then euthanized and their brains were dissected to remove the hippocampus and prefrontal cortex (PFC). Whole blood was collected to assess systemic oxidative stress. ROS and PIC mRNA and protein elevation in the PTSD group were normalized with VA. Anxiety decreased in this group via improved performance on the elevated plus-maze (EPM). No changes were attributed to VA in the control group, and no improvements were noted in the vehicle groups. Results indicate VA can attenuate oxidative stress and inflammation, enhance fear extinction, and correct neurotransmitter aberrancies in a rat model of PTSD.
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: C Brad
authors.initials: CB
authors.lastname: Wilson
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA. Electronic address: lmclaughlin@vetmed.lsu.edu.
authors.forename: Leslie D
authors.initials: LD
authors.lastname: McLaughlin
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Ebenezer
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Anand R
authors.initials: AR
authors.lastname: Nair
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA. Electronic address: jfrancis@vetmed.lsu.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Francis
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D002415:Cats; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011235:Predatory Behavior; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000503:physiopathology*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D016328:NF-kappa B; D012701:Serotonin; D014635:Valproic Acid; D009638:Norepinephrine
keywords: Anxiety; HDAC; Inflammation; Norepinephrine; PTSD; Serotonin