Excitatory Amino Acid Receptor Antagonist in Murine Motoneuron Disease (The Wobbler Mouse)

: Recent evidence has suggested a potential role for involvement of excitatory amino acids (EAA) in the pathogenesis of the neuron loss in motoneuron diseases. We have examined the ability of an antagonist of N-methyl-D-aspartate (NMDA) receptors to halt or retard the progression of neurological symptoms in a murine form of motoneuron disease. The wobbler mouse is an autosomal recessive mutant which develops progressive neurological symptoms secondary to motoneuron loss. Treatment of wobbler mice with the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5, 10-imine maleate (MK-801) did not retard neurological deterioration as assessed by a semiquantitative clinical scale. We conclude that NMDA receptor activation is probably not involved in the pathogenesis of motoneuron loss in the wobbler mouse.