Increased sensitivity of mice to tremorogenic agents following MPP+.
The behavioral effects following intrastriatal MPP+, the neurotoxic metabolite of MPTP, were evaluated in mice. Bilateral injections of 10 micrograms MPP+ to mice previously trained in the shuttle box paradigm produced a 66% decrease in striatal dopamine and significant deficits in all measures of conditioned avoidance responding. In addition, although these mice showed no deficits in baseline rotorod performance, challenge with the cholinergic agonist oxotremorine revealed that MPP+-treated mice exhibited an increased sensitivity to the disruptive effects of the drug at each dose and time point. Finally, MPP+-treated mice also exhibited an increase in tremor induced by 0.1 and 0.15 mg/kg oxotremorine. These observations are discussed in reference to idiopathic parkinsonism.