Influence of Redox and Dopamine Regulation in Cocaine-Induced Phenotypes Using .

Reactive Oxidative Species (ROS) are produced during cellular metabolism and their amount is finely regulated because of negative consequences that ROS accumulation has on cellular functioning and survival. However, ROS play an important role in maintaining a healthy brain by participating in cellular signaling and regulating neuronal plasticity, which led to a shift in our understanding of ROS from being solely detrimental to having a more complex role in the brain. Here we use to investigate the influence of ROS on behavioral phenotypes induced by single or double exposure to volatilized cocaine (vCOC), sensitivity and locomotor sensitization (LS). Sensitivity and LS depend on glutathione antioxidant defense. Catalase activity and hydrogen peroxide (HO) accumulation play a minor role, but their presence is necessary in dopaminergic and serotonergic neurons for LS. Feeding flies the antioxidant quercetin completely abolishes LS confirming the permissive role of HO in the development of LS. This can only partially be rescued by co-feeding HO or the dopamine precursor 3,4-dihydroxy-L-phenylalanine (L-DA) showing coordinate and similar contribution of dopamine and HO. Genetic versatility of can be used as a tool for more precise dissection of temporal, spatial and transcriptional events that regulate behaviors induced by vCOC.