Effects of serotonin depletion on the hippocampal GR/MR and BDNF expression during the stress adaptation.
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 (6h/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.
Zhou
Jiansong
J
Mental Health Institute of the 2nd Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha 410011 Hunan, China.
Li
Lingjiang
L
Tang
Shaojun
S
Cao
Xia
X
Li
Zexuan
Z
Li
Weihui
W
Li
Changqi
C
Zhang
Xianghui
X
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005518:Food Preferences / Q000187:drug effects / Q000523:psychology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012149:Restraint, Physical / Q000379:methods / Q000523:psychology; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage / Q000633:toxicity; D013315:Stress, Psychological / Q000503:physiopathology*; D010133:p-Chloroamphetamine / Q000008:administration & dosage / Q000633:toxicity
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D018490:Serotonin Agents; D012701:Serotonin; D010133:p-Chloroamphetamine