Neurotoxicity of methamphetamine

Abstract

Recreational consumption of the highly addictive psychostimulant methamphetamine is becoming a serious public health problem worldwide. Recent estimates indicate that methamphetamine abuse has increased in the last decade and that only cannabis is used by a greater number of consumers. Despite its popularity, methamphetamine is a known neurotoxin that damages dopaminergic terminals in the striatum, as indicated by reductions in striatal levels of dopamine and its metabolites and a sustained decrease in the expression of markers for dopaminergic terminals such as TH and DAT. In addition, methamphetamine affects the cell bodies of these same dopaminergic neurons in the substantia nigra, resulting in cell loss. The mechanisms underlying dopaminergic neurotoxicity are the focus of intense research, and knowledge in this area has expanded in recent decades. Evidence from previous studies points to dysregulation of dopamine, oxidative stress, DNA damage, and mitochondrial dysfunction as the main causes of methamphetamine neurotoxicity. The dopamine receptors D1 and D2 also play an important role in methamphetamine-induced neurotoxicity since inactivation of either receptor is neuroprotective against methamphet- amine. Recent results from clinical research indicate that methamphetamine abusers have a higher risk of developing Parkinson's disease; this is in keeping with results in laboratory animals and confirms the persistence of methamphetamine-induced dopaminergic injury. These findings suggest that neuroprotective strategies that are effective against methamphetamine-induced toxicity are also promising candidates for preventive therapy for Parkinson's disease and other persistent dopaminergic injuries.