Advances in drug addiction research using Caenorhabditis elegans: behavioral and molecular mechanisms.

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.

Study at a glance

Abstract

Drug addiction is a complex, chronic, and relapsing neurological disorder characterized by persistent neuroadaptation and a substantial public health burden. Because of its simple nervous system, genetic tractability, short life cycle, transparent body, and quantifiable behavioral phenotypes, C. elegans (Caenorhabditis elegans) has become a useful complementary model for studying selected aspects of drug-induced behavioral adaptation. This review summarizes recent advances in the use of C. elegans to study opioids, amphetamine-type stimulants, cocaine, ketamine, ethanol, nicotine, and related anesthetic or depressant-type compounds. We discuss commonly used behavioral paradigms, including conditioned cue preference, swimming-induced paralysis, tolerance assays, withdrawal-like responses, chemotaxis, and locomotor adaptation, together with dopaminergic, cholinergic, serotonergic, gamma-aminobutyric acid (GABA)-mediated, neuropeptidergic, ion-channel, oxidative-stress, transcriptional, and epigenetic mechanisms. The main limitations of this model are also considered, including the lack of mammalian reward-circuit complexity, nematode-specific pharmacokinetic features, cuticle permeability, and limited direct translational validation. Overall, C. elegans is best used as a mechanistic and screening-level model to identify conserved pathways and candidate targets that require further validation in mammalian systems.