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 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.
Wang
H-N
HN
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Peng
Y
Y
Tan
Q-R
QR
Chen
Y-C
YC
Zhang
R-G
RG
Qiao
Y-T
YT
Wang
H-H
HH
Liu
L
L
Kuang
F
F
Wang
B-R
BR
Zhang
Z-J
ZJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy*; D003072:Cognition Disorders / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004597:Electroshock; D004986:Ether / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy*; D013550:Swimming; D014474:Unconsciousness / Q000139:chemically induced
D018685:Anesthetics, Inhalation; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D004986:Ether; D000069348:Quetiapine Fumarate; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3