Cognitive changes in mice following moderate MPTP exposure.

We evaluated the cognitive effects of two moderate doses (30 mg/kg x 3 every 12 h and 20 mg/kg x 6 every 8 h, i.p.) of 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in mice. The dose of 30 mg/kg x 3 caused about 60% depletion of striatal dopamine but did not reduce the levels of its metabolites. Mice treated with MPTP did not differ from controls in their motor behavior in the open field. Mice treated with MPTP were comparable to controls in T-maze delayed alternation with fixed delays but were impaired when trials with mixed 20 s and 120 s delays were presented, indicative of a spatial working memory impairment. Dexmedetomidine at 10 microg/kg (s.c.) slightly improved delayed alternation performance in all groups but also slowed initiation of the motor response. Mice treated with MPTP at the dose of 30 mg/kg x 3 were less sensitive to this adverse effect of dexmedetomidine. The impairment in spatial working memory after MPTP exposure in mice parallels the findings in monkeys, but the deficit is much less severe.