Robotics may help unravel the biological determinants of substance use disorders: studies in zebrafish

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1. SUMMARY Substance use disorders (SUDs), the continuous use of substances in spite of negative consequences for the individual (withdrawal symptoms, social and functional impairments), constitutes a major societal and economical burden. While many individuals experience with drugs, only few develop SUDs: understanding the fundamental mechanisms regulating the transition from use to abuse constitutes a major challenge in biomedical sciences. Both genetic and environmental factors have been proposed to play a crucial role; yet, their precise contribution has remained elusive. Preclinical studies may bridge this gap as they allow for dissecting the role of several independent variables. Zebrafish are gaining momentum as a laboratory animal species as they have: a fully sequenced genome; a short intergeneration time; and a rapid adaptability to different environments. Despite their potential for gene x environment interaction studies, experimental paradigms addressing the consequences of drug exposure rest upon scoring two-dimensional (2D) trajectories, even though zebrafish swim in 3D. To modulate emotional responses, these paradigms often use live stimuli, which may represent inconsistent stimuli, thereby favoring experimental bias. Finally, social behavior is scored through methods that investigate group variables, but fail to quantify the behavior exhibited by an individual subject swimming in a group. Herein, we will bridge these gaps through an innovative robotics- enabled platform, coupled with a 3D tracking system to automatically investigate zebrafish individual and social behavior. The latter will allow for investigating how a single individual – exposed to ethanol, sedatives, or stimulants – behaves in isolation, or once introduced in a group of untreated shoal-members. Technological and methodological advances, to be freely disseminated to the scientific community, will enable hypothesis- driven experiments aimed at investigating the fundamental mechanisms governing SUD. These aims will be achieved through a multidisciplinary effort bridging engineering and behavioral neuroscience.