Identification of biochemical and cytotoxic markers in cocaine treated PC12 cells

Cocaine is one of the powerful addictive drugs, widely abused in most Western countries. Because of high lipophilic nature, cocaine easily reaches various domains of the central nervous system (CNS) and triggers different levels of cellular toxicity. The aim of this investigation was to reproduce cocaine toxicity in differentiated PC12 cells through quantitative knowledge on biochemical and cytotoxicity markers. We differentiated the cells with 0.1 μg/ml nerve growth factor (NGF) for 5 days, followed by treatment with cocaine for 48 h at in vivo and in vitro concentrations. Results indicated that cocaine at in vivo concentrations neither killed the cells nor altered the morphology, but decreased the mitochondrial membrane potential that paralleled with increased lactate and glutathione (GSH) levels. On the other hand, cocaine at in vitro concentrations damaged the neurites and caused cell death, which corresponded with increased reactive oxygen species (ROS) generation, plasma membrane damage, and GSH depletion with no detectable nitric oxide (NO) level. While direct understanding of cocaine and cell interaction under in vivo animal models is impeded due to high complexity, our present in vitro results assisted in understanding the onset of some key events of neurodegenerative diseases in cocaine treated neuronal cells.