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- Title
Activation of postsynaptic 5-HT receptors improve stress adaptation.
- Authors
Zhou, Jiansong; Cao, Xia; Mar, Adam; Ding, Yu-Qiang; Wang, Xiaoping; Li, Qi; Li, Lingjiang
- Abstract
Rationale: Serotonin-1A (5-HT) receptors modulate the stress response and have been implicated in the etiology and treatment of depression and anxiety disorders. A reduction in postsynaptic 5-HT receptor function in limbic areas has consistently been observed following exposure to chronic stress. Objectives: To investigate the hypothesis that increased activation of 5-HT receptors in rats having reduced 5-HT function may improve stress adaptation and the behavioral sequelae commonly associated with chronic stress. Methods: One hundred forty-four Sprague-Dawley rats received injections of para-chlorophenylalanine to partially deplete 5-HT then were given daily systemic pretreatment with the 5-HT receptor agonist, 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH-DPAT), the antagonist, WAY 100635, or vehicle prior to either restraint stress (6 h/day for 10 daily sessions) or control conditions. Anxiety- and depressive-like behaviors were then assessed using the open field and sucrose preference tests. Protein level of hippocampal glucocorticoid receptors (GR) and mineralocorticoid receptors was detected by immunohistochemistry and brain-derived neurotrophic factor (BDNF) was determined by in situ hybridization. Results: 8-OH-DPAT pretreatment prior to stress exposure attenuated later stress-induced anxiety- and depression-like behaviors and increased GR and BDNF mRNA expression in the hippocampus relative to vehicle- and WAY 100635-pretreated, stressed animals. Conclusion: The stress-related impairments associated with 5-HT deficiency can be improved by 8-OH-DPAT pretreatment prior to stress exposure and are associated with an augmentation of GR-like immunoreactivity and BDNF mRNA expression in the hippocampus. It suggested that selective activation of 5-HT receptors may be a potential treatment strategy for stress-related disorders such as anxiety and depression.
- Subjects
PSYCHOPHARMACOLOGICAL research; SEROTONIN; NEUROTRANSMITTERS; ADRENERGIC receptors; NEURAL receptors; PSYCHOLOGICAL stress research; GLUCOCORTICOID receptors
- Publication
Psychopharmacology, 2014, Vol 231, Issue 10, p2067
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-013-3350-z