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.

Public Health Relevance

While many individuals experience with drugs over the course of a lifetime, only a limited proportion of them develop substance use disorders (the continuous use of a substance despite overt consequences for the individual). Preclinical studies conducted in laboratory animals may help deciphering the factors bridging use to misuse and thereby greatly benefit patients and their relatives. In the present study, we will develop and validate an innovative engineering-enabled, robotics-assisted framework to study substance use disorders in zebrafish.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DA042558-01A1
Application #
9335106
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Grant, Steven J
Project Start
2017-08-01
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
New York University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Ruberto, Tommaso; Clément, Romain J G; Spinello, Chiara et al. (2018) The Tagging Procedure of Visible Implant Elastomers Influences Zebrafish Individual and Social Behavior. Zebrafish 15:433-444