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Memantine Disrupts Motor Coordination through Anxiety-like Behavior in CD1 Mice
Anton N Shuvaev1, Olga S Belozor1, Oleg I Mozhei2
1Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University Named after Prof. V.F. Voino-Yasenetsky, 660022 Krasnoyarsk, Russia.
Abstract:
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.
Insights
Memantine, used for Alzheimer's, may cause anxiety and behavioral despair in mice. This impacts motor performance tests and requires consideration in clinical trials.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Memantine is FDA-approved for Alzheimer's disease, targeting NMDA receptors to reduce neurodegeneration.
- Previous studies suggest memantine's potential neuroprotective effects in cerebellar conditions like spinocerebellar ataxia type-1 (SCA1).
- The impact of NMDA receptor blockers on anxiety necessitates careful evaluation of memantine's side effects.
Purpose of the Study:
- To investigate the chronic effects of memantine on anxiety-related behaviors and motor performance in CD1 mice.
- To assess potential adverse effects of memantine beyond its known therapeutic actions.
Main Methods:
- Chronic administration of memantine to CD1 mice over a 9-week period.
- Evaluation of rotarod performance to assess motor coordination and balance.
- Assessment of anxiety-related behaviors using tests such as the tail suspension test.
Main Results:
- Memantine-treated mice showed impaired adaptation to anxiety-provoking situations, significantly affecting rotarod performance.
- Increased signs of behavioral despair were observed in the tail suspension test.
- These findings suggest memantine may induce deleterious effects related to stress and adaptation.
Conclusions:
- Chronic memantine use may lead to maladaptive responses to stress, impacting motor function assessments.
- The observed behavioral changes warrant careful consideration during clinical trials involving memantine.
- Further research is needed to fully understand the side effect profile of memantine in diverse patient populations.
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