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Activation of postsynaptic 5-HT1A receptors improve stress adaptation

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Abstract

Rationale

Serotonin-1A (5-HT1A) receptors modulate the stress response and have been implicated in the etiology and treatment of depression and anxiety disorders. A reduction in postsynaptic 5-HT1A receptor function in limbic areas has consistently been observed following exposure to chronic stress.

Objectives

To investigate the hypothesis that increased activation of 5-HT1A 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-HT1A 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-HT1A receptors may be a potential treatment strategy for stress-related disorders such as anxiety and depression.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (30800368, 30470621, and 30670751). The experiments comply with the current laws of the People’s Republic of China.

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Authors and Affiliations

  1. Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Jiansong Zhou, Yu-Qiang Ding, Xiaoping Wang & Lingjiang Li

  2. Hunan Province Technology Institute of Psychiatry, Changsha, Hunan, 410011, China

    Jiansong Zhou & Xiaoping Wang

  3. Key Laboratory of Psychiatry and Mental Health of Hunan Province, Changsha, Hunan, 410011, China

    Jiansong Zhou & Xiaoping Wang

  4. Department of Health Management Center, the Third Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Xia Cao

  5. Department of Psychology Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge, UK

    Adam C Mar

  6. Department of Psychiatry, University of Hong Kong, Pok Fu Lam, Hong Kong

    Qi Li

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  1. Jiansong Zhou
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  2. Xia Cao
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  4. Yu-Qiang Ding
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Correspondence to Lingjiang Li.

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Zhou, J., Cao, X., Mar, A.C. et al. Activation of postsynaptic 5-HT1A receptors improve stress adaptation. Psychopharmacology 231, 2067–2075 (2014). https://doi.org/10.1007/s00213-013-3350-z

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  • DOI: https://doi.org/10.1007/s00213-013-3350-z

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