Opioid and Endocannabinoid Signaling Modulate Food Preference in C. Elegans
Kim AT, Li S, Kim Y, You YJ, Park Y. Food preference-based screening method for identification of effectors of substance use disorders using Caenorhabditis elegans. Life Sci 2024;345:122580. doi: 10.1016/j.lfs.2024.122580.
Background: Substance use disorders (SUD) affect millions globally and involve complex behavioral and neurochemical mechanisms. Opioid and endocannabinoid systems are key mediators of hedonic feeding and reward, but identifying effectors influencing these systems remains challenging. Caenorhabditis elegans, a model organism with conserved neurotransmission pathways, offers a simple platform to study such behaviors through quantifiable assays of food preference.
Hypothesis: This study hypothesized that modulation of opioid and cannabinoid receptors would alter C. elegans food preference behavior, enabling development of a screening assay to identify potential effectors of substance use–related systems.
Methods: The authors developed a binary food preference assay in C. elegans, assessing preference for high-quality (E. coli HB101) versus low-quality (Bacillus megaterium) food. They employed the WormLab Imaging System and WormLab to measure locomotion and analyze behavioral data. Wild-type, mutant and humanized strains expressing human μ-opioid receptor (MOPR) or cannabinoid 1 receptor (CB1R) were treated with known receptor agonists and antagonists.
Results: C. elegans preferred E. coli HB101 (preference index ≈0.2). Loperamide and ACEA (MOPR and CB1R agonists) increased, while naloxone and rimonabant decreased the preference index in receptor-dependent manners. Dopaminergic, serotonergic and olfactory mutants retained these responses. Humanized strains phenocopied wild-type results. Esculetin and L-theanine decreased preference via MOPR and CB1R, respectively.
Conclusions: Opioid and endocannabinoid signaling modulate food preference in C. elegans. This validated assay provides a rapid, behavior-based screening tool to identify modulators of MOPR and CB1R with translational potential for substance use disorder research.
