Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment

- The MPTP + probenecid (MPTPp) paradigm is a successful model of Parkinson's disease.
- MPTPp caused significant and replicable hyperactivity in adult male mice.
- Addition of a 1% trehalose solution did not prove neuroprotective.
- Tests of olfaction, grip strength, exploration, water maze performance were also unaffected.

The chronic MPTP + probenecid treatment paradigm has been used to successfully model the neurochemical, neuropathological, and behavioral effects associated with Parkinson's disease. Here, adult male C57Bl/6 mice were injected ip with 25 mg/kg MPTP and 250 mg/kg probenecid (MPTPp) or saline twice weekly for a total of 10 injections. Behavioral assessments included motor coordination, grip strength, spatial learning/memory, locomotor activity, and anhedonia. Those assessments were repeated up to 8 weeks post-treatment. In a subsequent experiment, adult male mice were treated with saline or MPTPp as described above. One-half of each group was allowed access to 1% trehalose in the water bottle. Trehalose intake averaged 1.90-2.34 g/kg. Behavioral assessments included locomotor activity, olfaction, motor coordination, grip strength, and exploratory behavior. Those assessments were repeated 4 weeks post-treatment. The strongest MPTPp effect was hyperactivity as exhibited in the open field. This increased activity was apparent in both experiments and occurred at all time points post-treatment. Assessments of grip strength, water maze performance, olfaction, and exploratory behavior did not indicate MPTPp-related alterations. When the specifications for the motor coordination test were made somewhat easier in the second experiment, there were deficits exhibited by the MPTPp group, the MPTPp + trehalose group and the trehalose group. The addition of trehalose did not alleviate any of the MPTPp-induced behavioral alterations; however, trehalose treatment significantly attenuated the striatal decreases in DA, DOPAC, HVA and 5-HIAA. These results provide a more comprehensive description of the behavioral alterations resulting from the chronic MPTPp treatment regimen and suggest that trehalose at this concentration does not act as a complete neuroprotectant.