Effects of amphetamines on mitochondrial function: role of free radicals and oxidative stress

Amphetamine-like psychostimulants are associated with long-term decreases in markers for monoaminergic neurons, suggesting neuronal loss and/or damage within the brain. This long-term "toxicity" results from formation of free radicals, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS), although the mechanism(s) of ROS and RNS formation are unclear. Mitochondria are a major source of ROS and mitochondrial dysfunction has been linked to some neurodegenerative disorders. Amphetamines also inhibit mitochondrial function, although the mechanism involved in the inhibition is,uncertain. This review coordinates findings on the multiple pathways for ROS and RNS and describes a hypothesis. involving mitochondrial inhibition in the initiation of amphetamine-induced cellular necrosis. (C) 2003 Elsevier Science Inc. All rights reserved.