RRC ID 80813
Author Kim AT, Li S, Kim Y, You YJ, Park Y.
Title Food preference-based screening method for identification of effectors of substance use disorders using Caenorhabditis elegans.
Journal Life Sci
Abstract Substance use disorder (SUD) affects over 48 million Americans aged 12 and over. Thus, identifying novel chemicals contributing to SUD will be critical for developing efficient prevention and mitigation strategies. Considering the complexity of the actions and effects of these substances on human behavior, a high-throughput platform using a living organism is ideal. We developed a quick and easy screening assay using Caenorhabditis elegans. C. elegans prefers high-quality food (Escherichia coli HB101) over low-quality food (Bacillus megaterium), with a food preference index of approximately 0.2, defined as the difference in the number of worms at E. coli HB101 and B. megaterium over the total worm number. The food preference index was significantly increased by loperamide, a μ-opioid receptor (MOPR) agonist, and decreased by naloxone, a MOPR antagonist. These changes depended on npr-17, a C. elegans homolog of opioid receptors. In addition, the food preference index was significantly increased by arachidonyl-2'-chloroethylamide, a cannabinoid 1 receptor (CB1R) agonist, and decreased by rimonabant, a CB1R inverse agonist. These changes depended on npr-19, a homolog of CB1R. These results suggest that the conserved opioid and endocannabinoid systems modulate the food preference behaviors of C. elegans. Finally, the humanoid C. elegans strains where npr-17 was replaced with human MOPR and where npr-19 was replaced with human CB1R phenocopied the changes in food preference by the drug treatment. Together, the current results show that this method can be used to rapidly screen the potential effectors of MOPR and CB1R to yield results highly translatable to humans.
Volume 345
Pages 122580
Published 2024-5-15
DOI 10.1016/j.lfs.2024.122580
PII S0024-3205(24)00169-3
PMID 38514005
MeSH Analgesics, Opioid / pharmacology Animals Caenorhabditis elegans* Drug Inverse Agonism Escherichia coli Food Preferences Humans Substance-Related Disorders* / drug therapy
C.elegans tm1392 tm1325 tm3210