PMID- 24258351 OWN - NLM STAT- MEDLINE DCOM- 20150221 LR - 20211021 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 231 IP - 10 DP - 2014 May TI - Activation of postsynaptic 5-HT1A receptors improve stress adaptation. PG - 2067-75 LID - 10.1007/s00213-013-3350-z [doi] AB - 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. FAU - Zhou, Jiansong AU - Zhou J AD - Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. FAU - Cao, Xia AU - Cao X FAU - Mar, Adam C AU - Mar AC FAU - Ding, Yu-Qiang AU - Ding YQ FAU - Wang, Xiaoping AU - Wang X FAU - Li, Qi AU - Li Q FAU - Li, Lingjiang AU - Li L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131121 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Piperazines) RN - 0 (Pyridines) RN - 0 (Serotonin 5-HT1 Receptor Agonists) RN - 0 (Serotonin 5-HT1 Receptor Antagonists) RN - 112692-38-3 (Receptor, Serotonin, 5-HT1A) RN - 333DO1RDJY (Serotonin) RN - 71IH826FEG (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide) RN - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin) RN - R5J7E3L9SP (Fenclonine) SB - IM MH - 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology MH - Adaptation, Psychological/drug effects/*physiology MH - Animals MH - Behavior, Animal/drug effects/physiology MH - Brain/drug effects/*metabolism MH - Fenclonine/pharmacology MH - Male MH - Motor Activity/drug effects/physiology MH - Piperazines/pharmacology MH - Pyridines/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Serotonin, 5-HT1A/metabolism MH - Serotonin/*metabolism MH - Serotonin 5-HT1 Receptor Agonists/pharmacology MH - Serotonin 5-HT1 Receptor Antagonists/pharmacology MH - Stress, Psychological/*metabolism EDAT- 2013/11/22 06:00 MHDA- 2015/02/24 06:00 CRDT- 2013/11/22 06:00 PHST- 2013/06/12 00:00 [received] PHST- 2013/10/28 00:00 [accepted] PHST- 2013/11/22 06:00 [entrez] PHST- 2013/11/22 06:00 [pubmed] PHST- 2015/02/24 06:00 [medline] AID - 10.1007/s00213-013-3350-z [doi] PST - ppublish SO - Psychopharmacology (Berl). 2014 May;231(10):2067-75. doi: 10.1007/s00213-013-3350-z. Epub 2013 Nov 21.