Effects of NMDA antagonists on the development and expression of tolerance to diazepam-induced motor impairment in mice

The goal of the study was to investigate the effects of ketamine and memantine on the development and expression of tolerance to diazepam (DZ)-induced motor impairment in mice. DZ-induced motor incoordination was assessed by the rotarod and chimney tests. It was found that (a) ketamine, at the dose of 5mg/kg (but not 2.5mg/kg), decreased the expression, but not the development, of tolerance to the motor impairing effects of DZ, (b) memantine, at the doses of 5 and 10mg/kg decreased both the development and expression of DZ tolerance in the rotarod test (also in the chimney test but at the higher dose of 10mg/kg) and (c) ketamine and memantine alone had no effect, either in the rotarod or the chimney test in mice. Those findings provided behavioral evidence that the glutamatergic system could contribute an important role in the development and/or expression of tolerance to DZ in mice.