DIGOXIN PREVENTS MPTP-INDUCED DOPAMINE DEPLETION IN MOUSE STRIATUM

Inhibition of Na+/K+ ATPase by cardiac glycosides has been shown to po tentiate toxic effects of excitatory amino acids and mitochondrial poi sons in neurons in vitro. The present study tested the hypothesis that the systemic administration of the cardiac glycoside, digoxin, potent iates effects of the dopamine neurotoxin 1-methyl-4-phenyl-1,2,5,6-tet rahydropyridine (MPTP) in vivo. Mice were injected with digoxin (1 mg/ kg) or vehicle followed by MPTP (20 mg/kg) or saline 1 h later. After 1 or 8 days, mice were euthanized and dopamine levels in the striatum were measured by high-performance liquid chromatography with electroch emical detection. MPTP caused a significant 35-45% reduction in striat al dopamine levels compared to those in control mice. However, pretrea tment with digoxin completely prevented the MPTP-induced dopamine depl etion. This result was unexpected and suggests that cardiac glycosides may protect against MPTP neurotoxicity. (C) 1997 Elsevier Science Inc .