Advances in drug addiction research using Caenorhabditis elegans: behavioral and molecular mechanisms.
Frontiers in Cell and Developmental Biology January 1, 2026 Lihua Yang, Shuang Wu, Jiale Liu et al.
The roundworm Caenorhabditis elegans serves as a useful complementary model for studying drug-induced behavioral adaptation due to its simple nervous system, genetic tractability, and quantifiable behaviors. This review covers recent work on opioids, amphetamines, cocaine, ketamine, ethanol, nicotine, and depressants using paradigms such as conditioned cue preference, swimming-induced paralysis, tolerance assays, withdrawal-like responses, chemotaxis, and locomotor adaptation. Mechanisms discussed include dopaminergic, cholinergic, serotonergic, GABA-mediated, neuropeptidergic, ion-channel, oxidative-stress, transcriptional, and epigenetic pathways. Limitations include the lack of mammalian reward-circuit complexity, nematode-specific pharmacokinetics, cuticle permeability, and limited translational validation. The authors propose C. elegans is best used as a mechanistic and screening-level model to identify conserved pathways needing further validation in mammals.