Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.
Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze (EPM) and forced swim tests (FST). We observed a decrease in the number of entries into open arms during the EPM (anxiety-like behavior) and increased immobility during the FST (depression-like behavior). When the PFC was removed after CRS and subject to western blot analysis, the GR expression reduced compared with control, while the levels of BDNF and its receptors remained unchanged. Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Shuichi
S
Chiba
Tadahiro
T
Numakawa
Midori
M
Ninomiya
Misty C
MC
Richards
Chisato
C
Wakabayashi
Hiroshi
H
Kunugi
D000818:Animals; D001007:Anxiety / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D003863:Depression / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D005938:Glucocorticoids / Q000097:blood; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012149:Restraint, Physical / Q000379:methods / Q000502:physiology / Q000523:psychology; D013315:Stress, Psychological / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D005938:Glucocorticoids; D009419:Nerve Tissue Proteins; D011965:Receptors, Glucocorticoid; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat; D018698:Glutamic Acid; D020813:Receptor, trkB