THE DOPAMINE-DEPLETING EFFECTS OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE IN CD-1 MICE ARE GENDER-DEPENDENT

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP) is a selective dopam inergic neurotoxin affecting the nigrostriatal system in a variety of species including, rodents, nonhuman primates and humans. There exists , however, a great deal of variability in the sensitivity of different species to the effects of MPTP. The present study was designed to det ermine whether a significant difference in gender susceptibility to th e toxin in CD-I mice might also exist. A dosing regiment of 30 mg/kg M PTP once a day for 3 days (90 mg/kg total dose) in 4-month-old male an d female CD-I mice led to a significant depletion of striatal dopamine in both sexes. Two way ANOVA analysis of a time-course generated by m easuring striatal dopamine at 4, 12 and 24 h after each dose of MPTP r evealed that the initial dopamine reduction is significantly greater i n male CD-1 mice (P < 0.001). Further, dopamine levels were reduced to a greater extent in male mice 5 days after the last dose (31% vs. 59% of control; P < 0.02). HPLC analysis using fluorescence detection rev ealed no difference in the striatal nor the cerebellar levels of MPP() between the two sexes, however, accumulation of larger amounts of MP P(+) was observed in the livers of the female mice. These findings sug gest that, while female CD-1 mice are more resistant to the dopamine-d epleting effects of MPTP, this gender difference is not due to decreas ed production or accumulation of striatal MPP(+).