Cell proliferation in the hippocampus and in the heart is modified by exposure to repeated stress and treatment with memantine

The present studies were aimed to verify the hypothesis that treatment with memantine, a low affinity NMDA glutamate receptor antagonist, can reduce possible stress-induced alterations in cell proliferation in the hippocampus and in the heart and has consequences on stress hormone release. Adult male Wistar rats were exposed to repeated hypokinesis (movement restraint, 2 h daily) or remained undisturbed and they were treated with memantine (5 mg/kg/day, s.c.) or vehicle for 8 days. On the day 7, all animals were injected with 5-bromo-2′-deoxyuridine (BrdU), a marker of cell proliferation. The mild form of chronic stress used resulted only in moderate decrease in BrdU incorporation into DNA in the hippocampus, while the same stimulus caused a pronounced reduction of the new cells formed in left heart ventricle. In both tissues, stress-induced reduction in cell proliferation was more evident in memantine-treated rats. Memantine failed to modify hormones of the hypothalamic-pituitary-adrenocortical axis, while the treatment increased plasma renin activity. The present study demonstrates that treatment with memantine potentiated rather than prevented stress-induced reduction of cell proliferation. We have shown that stress exposure may induce a reduction in cell proliferation in the heart, even in a higher extent than that in the hippocampus. Effects of memantine under stress conditions might be relevant with respect to clinical use of memantine, which is being used in the treatment of neurodegenerative diseases.