Synthetic cannabinoid receptor agonists (SCRA) and their impact on social interaction in juvenile zebrafish (Danio rerio)

• Grant number: 24/22077-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: April 01, 2025
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: José Luiz da Costa
• Grantee: Laura de Souza Borbi
• Supervisor: Randall Theodore Peterson
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Utah (U), United States
• Associated to the scholarship: 24/08365-2 - Toxicity and biotransformation studies of the synthetic cannabinoid ADB-INACA using zebrafish (Danio rerio) as an in vivo model, BP.IC

Abstract

New Psychoactive Substances (NPS) are compounds used for reasons similar to traditional illicit drugs, recognized for their pleasurable and therapeutic effects. Among these substances are the Synthetic Cannabinoid Receptor Agonists (SCRAs), which act as direct agonists of the CB1 and CB2 receptors. While THC is a partial agonist of the CB1 receptor, SCRAs exhibit higher toxicity due to their full agonist action on these receptors. ADB-INACA, a precursor to other SCRAs like ADB-PINACA, currently lacks data on its toxic effects and is not controlled in the United States of America (USA). Zebrafish (Danio rerio) have become widely used in Toxicology for behavioral research at both larval and adult stages, with validated assays available to study behaviors related to memory, anxiety, and conditioning.The Peterson lab pioneered large-scale social behavior assays, including Fishbook, an automated system that quantifies social behavior in zebrafish using a scoring system based on visual preference for conspecifics. By testing multiple fish simultaneously in a 3D-printed arena, it provides high-throughput reliable data. Thistest was capable to identify that embryonic exposure to Top2a chemical inhibitors leads to persistent social deficits in zebrafish and mice. By applying machine learning with ZeChat, they created social behavior profiles for numerous neuroactive compounds, discovering a social stimulative effect with dopamine D3 receptoragonists. Fishbook could be a valuable tool to investigate how ADB-INACA influences the development of important social behaviors like sociability, offering potential for faster and more reliable diagnosis in related cases of intoxication.