Neurotoxicity in psychostimulant and opiate addiction

Abstract

Psychostimulants and opioids evoke toxicity within the central nervous system (CNS), primarily linked to action of the substance (e.g., enhancement of synaptic concentrations of dopamine) or by indirect effects (increases in extrasynaptic glutamate levels, toxic metabolites). Associated with the development of drug addiction, the above mechanisms lead to the several pathological processes within the complex network of brain cell-to-cell interactions, such as alteration in neurotransmitter systems, dysrégulation of energy metabolism, changes in structure of cellular membrane, apoptosis, generation of reactive species (RS), glial/microglial cell overactivation, excitotoxicity and prominent deficits in brain morphology (neuronal loss, axonal damage), alterations of transcription factors, immediate early genes and epigenetic mechanisms, as well as neurocognitive and neuropsychological impairments.