Age-dependent effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): correlation with monoamine oxidase-B.

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration on whole brain dopamine content and monoamine oxidase subtype B (MAO-B) activity were assessed in Swiss-Webster male mice. Groups of mice at six different ages (1,2,4,8,16, and 52 weeks) were treated with either MPTP (12.5 mg/kg) every 2 hours for four subcutaneous injections or with the saline vehicle in the same injection volume. A third group of subjects was untreated and sacrificed at the same ages. The animals were sacrificed 1 week following treatment. The brains were removed and divided into right and left halves. The right brain halves from all subjects of a given age were assayed for MAO-B activity. The left brain halves were assayed for dopamine content using high performance liquid chromatography. The results revealed a significant age-dependent increase in both dopamine content and MAO-B activity in the untreated controls. It was also found that the toxic effect of MPTP as measured by whole brain dopamine depletion was increased at each successive age tested. There was a significant correlation (r = +0.96) between the baseline levels of MAO-B activity and the degree of lesion induced by MPTP treatment. These results indicate that the increased sensitivity to MPTP reported in aged animals may, in part, be attributable to the increase in MAO-B activity in older animals.