Ovarian steroids and raloxifene prevent MPTP-induced dopamine depletion inmice

The activity of steroids was studied in 1-methyl-4-phenyl-1,2,3,6-tetrahydr opyridine (MPTP) lesioned retired breeder C57BL/6 male mice as a model of P arkinson's disease. Steroids were injected daily for 5 days before MPTP (4 injections, 15 mg/kg i.p., at 2 h intervals) and hormonal treatment continu ed for 5 more days. Mice that received 17 beta-estradiol or progesterone or raloxifene (a selective estrogen receptor modulator) and MPTP had striatal concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) similar to those in control animal s, whereas mice that received MPTP alone or with 17 alpha-estradiol (the is omer with weak estrogenic activity) had an extensive decrease of DA and its metabolites. These results suggest stereospecific prevention of MPTP-induc ed dopamine loss by 17 beta-estradiol, which is also observed with progeste rone and raloxifene. NeuroReport 11:343-346 (C) 2000 Lippincott Williams & Wilkins.