Memantine Disrupts Motor Coordination through Anxiety-like Behavior in CD1 Mice

Memantine Disrupts Motor Coordination through Anxiety-like Behavior in CD1 Mice

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 are...

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Published in:Brain sciences Vol. 12; no. 4; p. 495
Main Authors: Shuvaev, Anton N, Belozor, Olga S, Mozhei, Oleg I, Mileiko, Aleksandra G, Mosina, Ludmila D, Laletina, Irina V, Mikhailov, Ilia G, Fritsler, Yana V, Shuvaev, Andrey N, Teschemacher, Anja G, Kasparov, Sergey
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 13-04-2022
MDPI
Subjects:
Alzheimer's disease
Animal models
Animals
Anxiety
ataxia
Ataxin
Behavior
Behavioral despair
Cerebellum
Cerebral cortex
Clinical trials
Glutamic acid receptors (ionotropic)
Laboratories
Memantine
Motor ability
Motor task performance
N-Methyl-D-aspartic acid receptors
Neurodegeneration
Neurodegenerative diseases
Neuronal-glial interactions
Noise
Patients
rotarod
Spinocerebellar ataxia
anxiety
ataxia
memantine
rotarod
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Summary: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.
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ISSN:2076-3425
2076-3425
DOI:10.3390/brainsci12040495