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: 6hours×28days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid...

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Published in:Progress in neuro-psychopharmacology & biological psychiatry 2012-10, Vol.39 (1), p.112-119
Main Authors: Chiba, Shuichi, Numakawa, Tadahiro, Ninomiya, Midori, Richards, Misty C., Wakabayashi, Chisato, Kunugi, Hiroshi
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Animals
Anxiety
Anxiety - blood
Anxiety - complications
Anxiety - metabolism
Anxiety - physiopathology
Behavior, Animal - physiology
Biological and medical sciences
Body weight gain
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor (BDNF)
Brain-Derived Neurotrophic Factor - metabolism
Brain-Derived Neurotrophic Factor - pharmacology
Cortex (prefrontal)
Depression
Depression - blood
Depression - complications
Depression - metabolism
Depression - physiopathology
Disease Models, Animal
Down-Regulation
Food intake
Glucocorticoid receptor
Glucocorticoid receptors
Glucocorticoids
Glucocorticoids - blood
Glutamic acid
Glutamic Acid - metabolism
High-performance liquid chromatography
Male
Medical sciences
Mood disorders
Neuropharmacology
Pharmacology. Drug treatments
Prefrontal cortex
Prefrontal Cortex - drug effects
Prefrontal Cortex - metabolism
Prefrontal Cortex - physiopathology
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Rats
Rats, Wistar
Receptor, trkB - metabolism
Receptors, Glucocorticoid - metabolism
Receptors, Nerve Growth Factor - metabolism
Restraint stress
Restraint, Physical - methods
Restraint, Physical - physiology
Restraint, Physical - psychology
Stress
Stress, Psychological - blood
Stress, Psychological - complications
Stress, Psychological - metabolism
Stress, Psychological - physiopathology
Sucrose
Western blotting
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Summary: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: 6hours×28days) 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 1week 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. ► Chronic restraint stress causes anxiety- and depression-like behavior in rats. ► Chronic stress reduces glucocorticoid receptor expression in rats' prefrontal cortex. ► Glutamate release after BDNF application is attenuated in chronically stressed rats. ► Parallel changes in behaviors and BDNF-dependent neural function are observed.
ISSN:0278-5846
1878-4216
DOI:10.1016/j.pnpbp.2012.05.018