Inhibition of N-methyl-D-aspartate receptor function appears to be
one of the common actions for antidepressants
Yun-Feng Li1*,
You-Zhi Zhang1,
Yan-Qin Liu1,
Heng-Lin Wang2,
Jiang-Bei Cao1,
Ting-Ting Guan1,
Zhi-Pu Luo1
1 Division of Psychopharmacology, Beijing Institute of Pharmacology and
Toxicology, Beijing, China
2 Department of Anesthesiology, 309 Hospital of Beijing, China
* To whom correspondence should be addressed.
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Abstract |
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In order to explore the possible common action mechanisms of three kinds of
classical antidepressants, inhibition of drugs on the N-methyl-D-aspartate
(NMDA)-Ca2-nitric oxide synthase (NOS) signal pathway was observed. With
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and lactic
dehydrogenase (LDH) assay, classical antidepressants, desipramine (1, 10 µM),
fluoxetine (0.625-10 µM) or moclobemide (2.5, 10 µM) antagonized NMDA
300 µM induced-lesion in PC12 cells. Using fura-2/AM (acetoxymethyl ester)
labelling assay, desipramine or fluoxetine at doses 1, 5 µM attenuated the
intracellular Ca2+ overload induced by NMDA 200 µM for 24 h in PC12
cells. Meanwhile, using confocal microscope, it was also found that desipramine 5
µM, fluoxetine 2.5 µM or moclobemide 10 µM decreased the NMDA
20 µM induced intracellular Ca2+ overload in primarily cultured rat
hippocampal neurons. Furthermore, desipramine (1, 5 µM), fluoxetine (1, 5
µM) or moclobemide (2.5, 10 µM) significantly inhibited NOS activity
in NMDA (300 µM) treated PC12 cells for 4 h. In summary, we suggest that
inhibition on the function of NMDA-Ca2+-NOS signal pathway appears to be one
of the common actions for antidepressants despite their remarkably different structures,
which is expected to have great implication for the evaluation and screening in
vitro of new antidepressants.
Key Words:
antidepressants, PC12 cells, N-methyl-D-aspartate, Ca2+
, nitric oxide synthase, hippocampal neurons
