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Effect of antidepressants on intracellular Ca++ mobilization in human frontal cortex
1Neurochemistry Department, National Institute of Mental Health and Neurosciences, Bangalore, India.
Background:
It is well documented that central serotonin (5-HT)2 receptor dysfunction is involved in the biochemistry and pathophysiology of depression and might be corrected by antidepressant drug treatment.
Methods:
The effect of imipramine (IMI) and fluoxetine (FLX) on 5-HT2A receptor-mediated intracellular calcium ([Ca++]i) mobilization in synaptosomes of human frontal cortex was studied. [Ca++]i was measured using Fura-2AM.
Results:
It was observed that in response to 5-HT (10 mumol/L) there was a significant increase (254%; p < .001) in [Ca++]i compared to basal level (140.00 +/- 31.77 nmol/L/mg protein). Both IMI and FLX (10-1000 nmol/L) induce mobilization of basal [Ca++]i in a dose-dependent manner. IMI and FLX antagonize the 5-HT-stimulated [Ca++]i mobilization in a dose-dependent manner. IMI showed higher antagonizing effect at lower concentration (10 nmol/L); however, FLX showed maximum antagonizing effect at higher concentration (1000 nmol/L).
Conclusions:
It is observed that imipramine and fluoxetine have different effects on antagonizing the 5-HT response in frontal cortex. One mode of action of these antidepressants might be by decreasing the intracellular calcium.