Evdokimov D. Neuroprotective activity of antidepressants.

It was shown that chronic administration of non-selective inhibitor of norepinephrine and serotonin reuptake, imipramine, selective inhibitor of serotonin reuptake, fluoxetine, and inhibitor of monoamine oxidase A, pirazidole, all at the dose of 20 mg/kg, possesses neuroprotective activity. Antidepressants decreased the inhibition of synaptic reactivity of pyramidal neurons of hippocampus and parietal cortex and granule neurons of dentate gyrus produced by synthetic glucocorticoid dexamethasone. Antidepressants decreased excitotoxic injury of pyramidal neurons of CA1 region and II/III layers of parietal cortex. Additionally, antidepressants decreased the inhibition of synaptic reactivity of pyramidal neurons of CA1 region and granule neurons of dentate gyrus produced by anoxia and aglycemia. Neuroprotective effects of antidepressants were associated with their ability to increase the expression of neurotrophic factor BDNF which involved in tyrosine kinase phosphorylation of neuronal substrates. The same effects were demonstrated for noncompetitive blocker of NMDA glutamate receptors, ketamine, and inhibitor of tyrosine phosphotases, sodium orthovanadate. Additionally, the neuroprotective activity of antidepressants was a consequence of down-regulation of NMDA receptors.