title: Early post-stressor intervention with minocycline, a second-generation tetracycline, attenuates post-traumatic stress response in an animal model of PTSD.
abstract: We assessed the effects of minocycline, a tetracycline with anti-inflammatory, anti-apoptotic and neuroprotective capacities, in an animal model of post-traumatic stress disorder (PTSD). Rats were exposed to psychogenic stress and treated 1h later with minocycline or saline. Behavioral measures included the elevated plus-maze (EPM) and acoustic startle response (ASR) 7 days post stress-exposure. One day after behavioral testing, animals were exposed to a trauma cue and freezing response was assessed. Local levels of cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus, frontal cortex (FC) and hypothalamus were then examined. Minocycline attenuated anxious-like behaviors in stress-exposed rats. In addition, decreased levels of cytokines were measured in exposed rats treated with minocycline compared to their counterparts treated with saline. This study suggests a potential use of minocycline in preventing physiological and behavioral alternations resulting from acute exposure to psychological stress. As this is the first study to report beneficial outcomes for minocycline treatment in an animal model of PTSD, further investigations of the use of minocycline in stress-related conditions with emphasis on PTSD is needed.
authors.affiliation: Beer-Yaakov Mental Health Center, Beer-Yaakov, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: yeheal@post.tau.ac.il.
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Levkovitz
authors.affiliation: Beer-Yaakov Mental Health Center, Beer-Yaakov, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Daphna
authors.initials: D
authors.lastname: Fenchel
authors.affiliation: Beer-Sheva Mental Health Center, Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Kaplan
authors.affiliation: Division of Psychiatry, Ministry of Health, The Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zohar
authors.affiliation: Beer-Sheva Mental Health Center, Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Cohen
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003463:Cues; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008911:Minocycline / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000150:complications*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology*; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D016207:Cytokines; D008911:Minocycline
keywords: Animal model; Interleukin-1 (IL-1); Interleukin-6 (IL-6); Minocycline; Post-traumatic stress disorder; Tumor necrosis factor-α (TNF-α)