Detection of Behavioral Impairments Correlated to Neurochemical Deficits in Mice Treated with Moderate Doses of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Abstract

Overt behavioral symptoms of Parkinson's disease (PD) do not occur until over 80% of the striatal dopamine content has been lost. Diagnosis of the disorder relies on identifying clinical symptoms including akinesia, resting tremor, and rigidity. In retrospect, behavioral deficits are observed several years prior to diagnosis. Behavioral manifestations in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, such as changes in general locomotor activity and rotorod performance, require large doses of MPTP and are often transient. We hypothesized that, as in PD, subtle behavioral changes also occur in the MPTP model. In this paper, we demonstrate that mice treated with moderate doses of the dopaminergic toxin MPTP display deficits in behavioral parameters that are significantly correlated with the loss of striatal dopamine. In addition, these behavioral measures are correlated to dopamine transporter, vesicular monoamine transporter, and tyrosine hydroxylase expression and are improved following l-DOPA administration. Detection of dopamine-modulated behavioral changes in moderately depleted MPTP mice will allow for more efficacious use of this model in PD research.