Quetiapine Ameliorates Anxiety-Like Behavior and Cognitive Impairments in Stressed Rats: Implications for the Treatment of Posttraumatic Stress Disorder

The purpose of this study was to determine preventive andprotective effects of chronic orally administration with quetiapine(QUE) against anxiety-like behavior and cognitive impairments inrats exposed to the enhanced single prolonged stress (ESPS), ananimal model that is used to study post-traumatic stress disorder(PTSD), and to detect changes in the expression of corticalphosphorylated p44/42 extracellular-regulated protein kinase(pERK1/2). Before or after exposure to ESPS paradigm,consisting of 2-h constraint, 20-min forced swimming, etherinduced loss of consciousness, and an electric foot shock, ratswere given orally QUE (10 mg/kg daily) for 14 days. Animalswere then tested in the open field (OF), elevated plus-maze(EPM), and Morris water maze (MWM). Brains were removed forimmunohistochemical staining of pERK1/2. ESPS exposureresulted in pronounced anxiety-like behavior compared tounexposed animals. ESPS-exposed animals also displayed markedlearning and spatial memory impairments. However, QUEtreatment (both before and after ESPS exposure) significantlyameliorated anxiety-like behavior, learning and spatial memoryimpairments. ESPS also markedly reduced the expression ofpERK1/2 in the prefrontal cortex, medial amygdala nucleus, andcingulate gyrus. Both before and after ESPS exposure QUEtreatments significantly elevated the reduced pERK1/2 expressionin the three brain regions. QUE has preventive and protectiveeffects against stress-associated symptoms and the changes inpERK1/2 functions may be associated with the pathophysiologyof traumatic stress and the therapeutic efficacy of anti-PTSDtherapy.