Cocaine as a neurotoxin

Abstract

Cocaine is a widely abused psychostimulant drug, with sympathomimetic properties and intense euphoric effects. Cocaine and some of its toxic metabolites cross the blood-brain barrier and induce neurologic impairments, affecting primarily the prefrontal cortex and basal ganglia. In this review, we discuss the mechanisms involved in brain dysfunction induced by cocaine, focusing on pre- and postsynaptic changes in dopaminergic and glutamatergic neurotransmission, oxidative stress, and mitochondrial dysfunction. Neurotoxic effects of combinations of cocaine with other drugs are also discussed. In summary, cocaine neurotoxicity may underlie brain dysfunction in cocaine and polydrug abusers and may predispose the brain to neurodegeneration.