The methamphetamine experience: a NIDA partnership

Abstract The neurotoxic properties of the amphetamines such as methamphetamine (METH) were originally described about the time of the National Institute on Drug Abuse’s organization, in the early 1970s. It required more than 20 years to confirm these neurotoxic properties in humans. Much like Parkinson’s disease, multiple high-dose administration of METH somewhat selectively damages the nigrostriatal dopamine (DA) projection of the brain. This effect appears to be related to the intracellular accumulation of cytosolic DA and its ability to oxidize into reactive oxygen species. Both the dopamine plasmalemmal transporter and the vesicular monoamine transporter-2 seem to play critical roles in this neurotoxicity. METH and related analogs such as methylenedioxymethamphetamine (MDMA) can also damage selective CNS serotonin neurons. The mechanism of the serotonergic neurotoxicity is not as well characterized, but also appears to be related to the formation of reactive oxygen species and monoamine transporters. Studies examining the pharmacological and neurotoxicological properties of the amphetamines have helped to elucidate some critical features of monoamine regulations as well as helped to improve our understanding of the processes associated with degenerative disorders such as Parkinson’s disease.