Neurotoxicity of cocaine

Abstract

Cocaine is a psychostimulant drug with sympathomimetic properties that is widelyabused. In the central nervous system, cocaine interacts with monoaminergic systems,which mediate many of the drug's effects. However, the interaction with thedopaminergic system is the main cause of cocaine's addictive effects. Cocaine shareschemical similarities with dopamine and binds to the dopamine transporter at the plasmamembrane of dopaminergic terminals, blocking dopamine re-uptake, resulting inincreased synaptic dopamine. Excess dopamine levels may induce oxidative stressthrough dopamine auto-oxidation, generating reactive oxygen species. Cocaine alsoaffects glutamate levels and the expression of glutamate receptors, which may mediateexcitotoxic cell damage. Interactions with these neurotransmission systems may underliecocaine neurotoxicity.Cocaine has also been shown to impair mitochondrial function in several models,namely through the inhibition of mitochondrial respiratory chain complex I and mayinduce the activation of mitochondrial apoptotic pathways. Cocaine is frequently coabusedwith heroin in a combination known as speedball. Indeed, heroin may modulate ormodify cocaine's effects.A chemical interaction between cocaine and morphine was found in drug mixturessimilar to those used by speedball abusers, which may have a specific neurotoxic profile.In addition, cocaine abuse shares some common aspects with neurodegenerativedisorders such as Parkinson's disease (PD), which also involves a dysfunction in thedopamine system. Thus, although neurotoxicity of cocaine may not be very pronounced,it may underlie brain dysfunction in cocaine and poly-drug abusers, which may predispose the brain to the development of neurodegenerative diseases.