Quetiapine ameliorates anxiety-like behavior and cognitive impairments in stressed rats: implications for the treatment of posttraumatic stress disorder

Physiol Res. 2010;59(2):263-271. doi: 10.33549/physiolres.931756. Epub 2009 Jun 19.


The purpose of this study was to determine preventive and protective effects of chronic orally administration with quetiapine (QUE) against anxiety-like behavior and cognitive impairments in rats exposed to the enhanced single prolonged stress (ESPS), an animal model that is used to study post-traumatic stress disorder (PTSD), and to detect changes in the expression of cortical phosphorylated p44/42 extracellular-regulated protein kinase (pERK1/2). Before or after exposure to ESPS paradigm, consisting of 2-h constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, rats were given orally QUE (10 mg/kg daily) for 14 days. Animals were then tested in the open field (OF), elevated plus-maze (EPM), and Morris water maze (MWM). Brains were removed for immunohistochemical staining of pERK1/2. ESPS exposure resulted in pronounced anxiety-like behavior compared to unexposed animals. ESPS-exposed animals also displayed marked learning and spatial memory impairments. However, QUE treatment (both before and after ESPS exposure) significantly ameliorated anxiety-like behavior, learning and spatial memory impairments. ESPS also markedly reduced the expression of pERK1/2 in the prefrontal cortex, medial amygdala nucleus, and cingulate gyrus. Both before and after ESPS exposure QUE treatments significantly elevated the reduced pERK1/2 expression in the three brain regions. QUE has preventive and protective effects against stress-associated symptoms and the changes in pERK1/2 functions may be associated with the pathophysiology of traumatic stress and the therapeutic efficacy of anti-PTSD therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Anxiety Disorders / drug therapy*
  • Cognition Disorders / drug therapy*
  • Dibenzothiazepines / pharmacology*
  • Disease Models, Animal
  • Electroshock
  • Ether / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Quetiapine Fumarate
  • Rats
  • Rats, Sprague-Dawley
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Swimming
  • Unconsciousness / chemically induced


  • Anesthetics, Inhalation
  • Antipsychotic Agents
  • Dibenzothiazepines
  • Ether
  • Quetiapine Fumarate
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3