SEX-RELATED EFFECTS OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDRO-PYRIDINE TREATMENT MAY BE RELATED TO DIFFERENCES IN MONOAMINE-OXIDASE-B

Effects of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) on striatal dopamine metabolism and the influence of sex on the recovery were investigated in adult (2-month-o ld) male and female C57/BL mice. We present here evidence that MPTP tr eatment (2 doses of 30 mg/kg i.p., each at 24 h interval) produced a s imilar reduction (-65% to -70%) of striatal dopamine in both sexes 24 h after the last injection of MPTP, and a greater loss of the metaboli tes in the female group. In contrast to the partial recovery observed in the male group, an increased dopamine loss occurred in the female g roup within 10 days following the last injection of MPTP. This impairm ent in recovery appears to be different to the one already observed in aged (24-month-old) male mice treated in similar conditions. As the n eurotoxic effects of MPTP depend on its conversion to the 1-methyl-4-p henylpyridinium ion (MPP(+)) by monoamine oxidase B (MAO B), the prese nce of a different peripheral or central MAO B type in female mice cou ld be in part responsible for these sex related effects. To investigat e this possibility, MAO A and B activities were characterized in liver and brain of adult female control mice during the different steps of the oestrous cycle and compared to those of adult control male mice. S ignificant differences in MAO A and MAO B activities could be detected during the oestrous cycle and between the adult male and female group s. It is concluded that MAO B may be involved in the sex related effec ts of MPTP.