Memantine is an FDA approved drug for the treatment of
Alzheimer's disease. It reduces neurodegeneration in the hippocampus and cerebral cortex through the inhibition of extrasynaptic
NMDA receptors in patients and mouse models. Potentially, it could prevent neurodegeneration in other brain areas and caused by other diseases. We previously used
memantine to prevent functional damage and to retain morphology of cerebellar neurons and Bergmann glia in an optogenetic mouse model of
spinocerebellar ataxia type-1 (
SCA1). However, before suggesting wider use of
memantine in clinics, its side effects must be carefully evaluated. Blockers of
NMDA receptors are controversial in terms of their effects on anxiety. Here, we investigated the effects of chronic application of
memantine over 9 weeks to CD1 mice and examined rotarod performance and anxiety-related behaviors.
Memantine-treated mice exhibited an inability to adapt to anxiety-causing conditions which strongly affected their rotarod performance. A tail suspension test revealed increased signs of behavioral despair. These data provide further insights into the potential deleterious effects of
memantine which may result from the lack of adaptation to novel, stressful conditions. This effect of
memantine may affect the results of tests used to assess motor performance and should be considered during clinical trials of
memantine in patients.