Protective effect of gan mai da zao decoction in unpredictable chronic mild stress-induced behavioral and biochemical alterations.
OBJECTIVE
Growing evidence indicates that the glutamatergic system, especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA) receptors contribute to the pathophysiology and possibly the pathogenesis of major depressive disorders. This study is to evaluate the effect of gan mai da zao (GMDZ) decoction on glutamate and NMDA receptor in unpredictable chronic mild stress (UCMS) rats.


METHODS
Sucrose preference test and open field test were used to estimate the depressive-like behaviors of UCMS rats. Glutamate levels and NMDA receptor subunits (NR1, NR2A and NR2B) in the frontal cortex and hippocampus were determined by HPLC-FLD and by western-blot respectively.


RESULTS
32 days UCMS induced depressive-like behaviors, increased glutamate concentration and decreased NMDA receptor subunits NR2A and NR2B in the frontal cortex and hippocampus of rats. However, NR1 expression remained constant in stressed rats compared with normal. The GMDZ decoction alleviated the depressive-like behavior, decreased glutamate level, and increased expression of NMDA receptor subunit NR2A and NR2B in the frontal cortex and hippocampus of stressed rats.


CONCLUSIONS
These results suggest that GMDZ treatment reversed chronic unpredictable stress-induced depressive-like behaviors in UCMS rats, possibly via reducing glutamate levels and increasing the NMDA receptor subunits NR2A and NR2B in frontal cortex and hippocampus.
Lou
Jian-Shu
JS
Center for Drug Safety Evaluation and Research, Medical College, Zhejiang University, Hangzhou, Republic of China.
Li
Chang-Yu
CY
Yang
Xiao-Chun
XC
Fang
Jie
J
Yang
Yuan-Xiao
YX
Guo
Jian-You
JY
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy*; D013395:Sucrose / Q000008:administration & dosage
D004365:Drugs, Chinese Herbal; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D013395:Sucrose