Advances in drug addiction research using <i>Caenorhabditis elegans</i>: behavioral and molecular mechanisms.

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, <i>C. elegans</i> (<i>Caenorhabditis elegans</i>) has become a useful complementary model for studying selected aspects of drug-induced behavioral adaptation. This review summarizes recent advances in the use of <i>C. elegans</i> 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, <i>C. elegans</i> is best used as a mechanistic and screening-level model to identify conserved pathways and candidate targets that require further validation in mammalian systems.

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