期刊
BEHAVIOURAL BRAIN RESEARCH
卷 195, 期 1, 页码 129-138出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2008.06.009
关键词
Hippocampus; Glucocorticoid receptor; BDNF; Stress; Adaptation
资金
- National Natural Science Foundation of China [30470621, 30670751]
- Chinese Academy of Sciences
- 973 program [2006CB500800]
- Chinese Science and Technology [2007BAI17B02]
Increased serotonin (5-hydroxytryptamine, 5-HT) release in the hippocampus induced by repeated stress is thought to be critical for the neuroadaptation that alleviates the adverse effects of stressors on emotion and behavior. A failure in this process may be one of the primary neuropathological mechanisms underlying the development of stress-related disorders. The para-chloroamphetamine (p-PCA) was used to deplete 5-HT in the rat prior to repeated restraint stress (6 h/day for 10 days), and determined the consequences of 5-HT depletion on stress-induced alterations of animal behaviors, hippocampal corticosteroid receptor immunoreactivity and the brain-derived neurotrophic factor (BDNF) mRNA expression. Behavioral tests indicate that the stressed rats with 5-HT depletion showed pronounced anxiety, reduced reward sensitivity and enhanced learned-helplessness. In addition, they also developed learning impairments in Morris water maze tests. These results suggest that hippocampal 5-HT depletion compromised adaptation to chronic stress. Furthermore, repeated stress caused a lesser degree of glucocorticoid receptor increase and down-regulation of BDNF mRNA. The study suggest that 5-HT deficiency in the adult hippocampus may impair stress adaptation by suppressing hippocampal GR and BDNF expression. (C) 2008 Elsevier B.V. All rights reserved.
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