Activity of the 5-HT1A receptor is involved in the alteration of glucocorticoid receptor in hippocampus and corticotropin-releasing factor in hypothalamus in SPS rats.
Rats exposed to single-prolonged stress (SPS) showed enhanced inhibition of the hypothalamic-pituitary-adrenal (HPA) system and alteration in the glucocorticoid/mineralocorticoid receptor. Dysfunction of the HPA axis is one of the core neuroendocrine abnormalities of post-traumatic stress disorder (PTSD). Serotonergic receptor, glucocorticoid receptor (GR) and corticotropin-releasing factor (CRF) have been proposed to play major roles in dysfunction of the HPA axis. However, the precise molecular mechanism is unknown. In this study, we investigated the relationships between the changes of GR in hippocampus as well as CRF in hypothalamus and the activity of 5-HT1A receptor in SPS rats. We exposed rats to SPS with or without prior treatment with WAY100635 (the 5-HT1A receptor antagonist), and observed behavioral changes, GR levels in the hippocampus and CRF levels in the hypothalamus by immunohistochemistry, Western blotting and RT-PCR seven days after SPS. Our results demonstrate that SPS increases expression of GR and CRF, which were partially inhibited by WAY-100635.
Wang
Hai-Tao
HT
Department of Histology and Embryology, Basic Medical Sciences College, China Medical University, Shenyang 110001, Liaoning Province, PR China.
Han
Fang
F
Shi
Yu-Xiu
YX
D000818:Animals; D015153:Blotting, Western; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012149:Restraint, Physical / Q000009:adverse effects / Q000523:psychology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D013550:Swimming / Q000523:psychology
D010879:Piperazines; D011725:Pyridines; D011965:Receptors, Glucocorticoid; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D003346:Corticotropin-Releasing Hormone