INCREASED EXPRESSION OF MONOAMINE OXIDASE-B RESULTS IN ENHANCED NEURITE DEGENERATION IN METHAMPHETAMINE-TREATED PC12 CELLS

In vivo administration of methamphetamine (MA) produces selective dama ge to dopaminergic nerve terminals, which is hypothesized to be due to release of dopamine from synaptic vesicles within the terminals, allo wing the generation of reactive oxygen species (ROS) via dopamine meta bolism, Hydrogen peroxide formed during this reaction can interact wit h free iron to form hydroxyl radicals, which can oxidize proteins, nuc leic acids, and membrane lipids, leading to terminal degeneration, Ele vation of activity of the dopamine-metabolizing enzyme monoamine oxida se (MAO) in nerve growth factor-treated PC12 cells resulted in a subst antial rise in products of dopamine metabolism following MA treatment, including 3,4-dihydroxyphenylacetic acid and hydroperoxides, as well as an increase in lipid peroxidation and a decrease in neurite number and length compared with control cells, These latter effects could be reversed by treatment with the MAO-B specific inhibitor, deprenyl, The se data suggest that dopamine metabolism and subsequent ROS production may be key elements in MA-induced neurite degeneration in dopaminergi c neurons. (C) 1997 Wiley-Liss, Inc.