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Interaction between redox status and psychostimulants-induced neuronal plasticity Drosophila

Addictive drugs engage mechanisms of neural plasticity to change the function and structure of the brain resulting in addiction. Molecular mechanisms of drug-induced neuroplasticity are only partially understood, and recent evidence suggests involvement of redox regulation. Our hypothesis is that if changes in redox status modulate neuronal plasticity, then this will be evident as a change in a form of neuroplastic change: locomotor sensitization to psychostimulants. To study the mechanisms of neuroplasticity in the lab, we use a model organism, Drosophila melanogaster, and we focus on a simple endophenotype: locomotor sensitization (LS) to cocaine (COC) and methamphetamine (METH) using our newly develop high throughput system, FlyBong. We induce LS using two administrations of the same dose of volatilized drug. To change redox status we feed flies for 16 hrs before drug exposure to one of the following substances: prooxidants hydrogen peroxide or paraquat, and antioxidants quercetin or tempol. To measure effects of treatment on redox status we measure activity of catalase and superoxide dismutase in the whole fly homogenates. We find that exposure to COC and METH alone increases activity of the antioxidant enzyme catalase and decreases activity of superoxide dismutase, while treatment with quercetine does the opposite. Interestingly, when COC or METH are combined with either pro- or antioxidant substances LS is abolished. However, LS is restored when pro- and antioxidants are given together, indicating that a proper balance of redox state is required for LS to develop. Our results indicate that redox state interacts with mechanisms of neural plasticity and that when balance is disturbed, LS does not develop. We are interested in defining those interactions, and defining consequences that redox-induced neuroplastic change have on rewarding aspects of psychostimulants that can be measured in self-administration paradigm.

neuronal plasticity, psychostimulants, redox, Drosophila melanogaster

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