Effects of Dopaminergic Agents and of an NMDA Receptor Antagonist on Motor Coordination in Lurcher Mutant Mice

Abstract

Lurcher mutant mice, characterized by an ataxic gait and olivocerebellar degeneration, were evaluated for motor coordination in the coat-hanger test after peripheral injections of two doses of dextromethorphan, a noncompetitive N-methyl- d-aspartate receptor antagonist, l-dopa/carbidopa, and SKF 77434, a dopamine D 1 receptor agonist. There was an improvement in the distance traveled on the suspended horizontal string after 25 and 50 mg/kg of dextromethorphan and 37.5 mg/kg of l-dopa/carbidopa, but not after SKF 77434. None of the drugs reduced movement times or increased latencies before falling. These results indicate that NMDA receptor antagonism or stimulation of some dopaminergic mechanisms partially improve genetically determined cerebellar ataxia in mice.