Background and Objective: Memantine is a glutamate N-Methyl-D-Aspartate (NMDA) receptor antagonist with low receptor binding affinity which is currently used in moderate to severe Alzheimer’s disease. So far, the effect of memantine on stress system has not been investigated. This study focused on the effects of both peripheral and intra-accumbal memantine administration on plasma corticosterone concentration in female NMRI mice.

Materials and Methods: Four groups of mice (n=6/group) received different doses of memantine (1, 0.5 and 0.1 mg/kg) intraperitoneally. In this groups were canulated bi- or unilaterally in the nucleus accumbens by stereotaxic instrument. After a week of recovery, memantine (1, 0.5 and 0.1 µg/kg mouse) was administrated to the animals intra-accumbally. Blood samples were taken from retro-orbital sinus of all animals 30 min (intraperitoneally administration) or 5 min (intra-accumbally) following memantine injection for the evaluation of plasma corticosterone.

Results: Intraperitoneal memantine injection led to a dramatic increase in plasma corticosterone concentration in a dose-independent manner. On the other hand, intra-accumbal memantine administrations increased plasma corticosterone level significantly (P<0.001) in a dose and site –dependent manner. 

Conclusion: Memantine may have a severe effect on stress system by virtue of plasma corticosterone level increment which may be the side effect of this medication.