title: Paroxetine treatment, following behavioral suppression of PTSD-like symptoms in mice, prevents relapse by activating the infralimbic cortex.
abstract: Clinical studies have shown that post-traumatic stress disorder (PTSD) remission, induced by selective serotonin reuptake inhibitor (SSRI) treatment, is associated with increased prefrontal activation during post-treatment symptom provocation. Other studies have shown that continuation SSRI treatment after remitting from PTSD reduces the rate of relapse. The aim of the present preclinical study was to investigate the relationship between post-treatment prefrontal changes and PTSD relapse prevention. Avoidance conditioning (with a 1.5-mA foot-shock), avoidance extinction and a trauma priming exposure (with a 0.3-mA foot-shock) were used in mice to induce, suppress and reactivate PTSD-like symptoms (including avoidance, fear sensitization, enhanced contextual fear, and anxiety-like behavior), respectively. Paroxetine, injected at 8 mg/kg/day (7 days), was used as SSRI treatment. PTSD-like symptoms were present for at least 30 days and resistant to paroxetine treatment. However, after extinction training (suppressing all PTSD-like symptoms), paroxetine treatment prevented symptom reactivation. Paroxetine treatment also induced infralimbic neuronal activation. However, infralimbic functional tetrodotoxin inactivation abolished the preventive effect of paroxetine treatment on symptom reactivation. The data reveal a potential ability of treatments inducing infralimbic activation to provide prophylactic protection against PTSD relapse.
authors.affiliation: Laboratoire de Pharmacologie, Neurobiologie et Comportement, Centre National de la Recherche Scientifique et Technique, URAC 37, Cadi Ayyad Université, Marrakech, Maroc.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Bentefour
authors.affiliation: Laboratoire de Pharmacologie, Neurobiologie et Comportement, Centre National de la Recherche Scientifique et Technique, URAC 37, Cadi Ayyad Université, Marrakech, Maroc.
authors.forename: Youness
authors.initials: Y
authors.lastname: Rakibi
authors.affiliation: Laboratoire de Pharmacologie, Neurobiologie et Comportement, Centre National de la Recherche Scientifique et Technique, URAC 37, Cadi Ayyad Université, Marrakech, Maroc.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bennis
authors.affiliation: Laboratoire de Pharmacologie, Neurobiologie et Comportement, Centre National de la Recherche Scientifique et Technique, URAC 37, Cadi Ayyad Université, Marrakech, Maroc.
authors.forename: Saadia
authors.initials: S
authors.lastname: Ba-M'hamed
authors.affiliation: Institut de Neurosciences de la Timone, UMR7289, Aix-Marseille Université & Centre National de la Recherche Scientifique, 13385 Marseille, France. Electronic address: rene.garcia@unice.fr.
authors.forename: René
authors.initials: R
authors.lastname: Garcia
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use; D001362:Avoidance Learning / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology* / Q000627:therapeutic use*; D012008:Recurrence; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D018687:Antidepressive Agents, Second-Generation; D016761:Oncogene Proteins v-fos; D017374:Paroxetine; D013779:Tetrodotoxin
keywords: Antidepressant; Infralimbic cortex; Mouse PTSD model; Relapse prevention