title: Escitalopram reversed the traumatic stress-induced depressed and anxiety-like symptoms but not the deficits of fear memory.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) is a trauma-induced mental disorder characterised by fear extinction dysfunction in which fear circuit monoamines are possibly associated. PTSD often coexists with depressive/anxiety symptoms, and selective serotonin reuptake inhibitors (SSRIs) are recommended to treat PTSD. However, therapeutic mechanisms of SSRIs underlying the PTSD fear symptoms remain unclear.
  
  
  OBJECTIVE
  Using a rodent PTSD model, we examined the effects of early SSRI intervention in mood and fear dysfunctions with associated changes of monoamines within the fear circuit areas.
  
  
  METHODS
  A 14-day escitalopram (ESC) regimen (5 mg/kg/day) was undertaken in two separate experiments in rats which previously received a protocol of single prolonged stress (SPS). In experiment 1, sucrose preference and elevated T-maze were used to index anhedonia depression and avoidance/escape anxiety profiles. In experiment 2, the percentage of freezing time was measured in a 3-day fear conditioning paradigm. At the end of our study, tissue levels of serotonin (5-HT) in the medial prefrontal cortex, amygdala, hippocampus, and striatum were measured in experiment 1, and the efflux levels of infralimbic (IL) monoamines were measured in experiment 2.
  
  
  RESULTS
  In experiment 1, ESC corrected both behavioural (depression/anxiety) and neurochemical (reduced 5-HT tissue levels in amygdala/hippocampus) abnormalities. In experiment 2, ESC was unable to correct the SPS-impaired retrieval of fear extinction. In IL, ESC increased the efflux level of 5-HT but failed to reverse SPS-reduced dopamine (DA) and noradrenaline (NA).
  
  
  CONCLUSIONS
  PTSD-induced mood dysfunction is psychopathologically different from PTSD-induced fear disruption in terms of disequilibrium of monoamines within the fear circuit areas.
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, 11490, Taiwan.
authors.forename: Chen-Cheng
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Medical Research and Education, Cheng Hsin General Hospital, Taipei, 11220, Taiwan.
authors.forename: Che-Se
authors.initials: CS
authors.lastname: Tung
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, 11490, Taiwan. yiaping@ms75.hinet.net.|Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, 11490, Taiwan. yiaping@ms75.hinet.net.
authors.forename: Yia-Ping
authors.initials: YP
authors.lastname: Liu
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005239:Fear / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Anxiety; Depression; Fear memory; Posttraumatic stress disorder; Selective serotonin reuptake inhibitor; Serotonin