Effects of dopaminergic agents and of an NMDA receptor antagonist on motorcoordination in Lurcher mutant mice

Lurcher mutant mice, characterized by an ataxic gait and olivocerebellar de generation, were evaluated for motor coordination in the coat-hanger test a fter peripheral injections of two doses of dextromethorphan, a noncompetiti ve N-methyl-D-aspartate receptor antagonist, L-dopa/carbidopa, and SKF 7743 4, a dopamine D-1 receptor agonist. There was an improvement in the distanc e traveled on the suspended horizontal string after 25 and 50 mg/kg of dext romethorphan and 37.5 mg/kg of L-dopa/carbidopa, but not after SKF 77434. N one of the drugs reduced movement times or increased latencies before falli ng. These results indicate that NMDA receptor antagonism or stimulation of some dopaminergic mechanisms partially improve genetically determined cereb ellar ataxia in mice. (C) 1999 Elsevier Science Inc.