The Fas Receptor/Fas-Associated Protein and Cocaine

This chapter summarizes the current data studying the effects of cocaine on altering the balance between the induction of aberrant apoptotic cell death (i.e., neurotoxicity) and nonapoptotic events (i.e., neuroplasticity) mediated through the activation of Fas receptor and Fas-associated protein (FADD) in the rat brain and the human postmortem brain. The findings presented here reveal important differences between humans and rats concerning the long-term regulation of the extrinsic apoptotic pathway by cocaine in the brain. The Fas/FADD complex is downregulated in the prefrontal cortex of human cocaine addicts, while it shows tolerance to an acute upregulation in the brain of cocaine-treated rats. The modulation of Fas receptor and more interestingly that of FADD adaptor by cocaine is a new and relevant molecular process in the complex neurobiology of cocaine addiction, suggesting long-term contraregulatory adaptations or nonapoptotic actions.