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

被引:49
作者
Wang, H. -N. [1 ]
Peng, Y. [1 ]
Tan, Q. -R. [1 ]
Chen, Y. -C. [1 ]
Zhang, R. -G. [1 ]
Qiao, Y. -T. [1 ]
Wang, H. -H. [1 ]
Liu, L. [2 ]
Kuang, F. [2 ]
Wang, B. -R. [2 ]
Zhang, Z-J. [3 ,4 ]
机构
[1] Fourth Mil Med Univ, Dept Psychiat, Xijing Hosp, 17 Changle Rd, Xian 710032, Shaanxi, Peoples R China
[2] Fourth Mil Med Univ, Inst Neurosci, Xian 710032, Shaanxi, Peoples R China
[3] Univ Hong Kong, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China
[4] Univ Hong Kong, Fac Med, Hong Kong, Hong Kong, Peoples R China
关键词
PTSD; Quetiapine; Anxiety; Cognitive impairment; ERK; SINGLE-PROLONGED STRESS; PHARMACOLOGICAL-TREATMENT; MESSENGER-RNA; OPEN TRIAL; SYMPTOMS; TRAUMA; MEMORY; NEUROBIOLOGY; PERFORMANCE; EXPOSURE;
D O I
10.33549/physiolres.931756
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:263 / 271
页数:9
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