Advances in drug addiction research using Caenorhabditis elegans: behavioral and molecular mechanisms.
Lihua Yang, Shuang Wu, Jiale Liu, Wenjun Wang, Qinhong Yin, Elizabeth Rosalind Thomas, Xiang Li
Frontiers in Cell and Developmental Biology 2026 DOI: 10.3389/fcell.2026.1880079 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Neuroplasticity Addiction |
| Keywords | Caenorhabditis elegans Behavioral changes Drug addiction Signaling |
| Key findings | Argues that 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. |
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.
Comparable studies
Other narrative reviews on addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Mindfulness meditation–based pain relief: a mechanistic account | 2016 | Review | |
| Psychedelics as anti-inflammatory agents Animal models and cellular studies | 2018 | Review | |
| A narrative review of yoga and mindfulness as complementary therapies for addiction. | 2013 | Review | |
| The neuropsychopharmacology of cannabis: A review of human imaging studies | 2018 | Review |
Citations in the library
Cites 2
- Utilizing Caenorhabditis Elegans as a Rapid and Precise Model for Assessing Amphetamine-Type Stimulants: A Novel Approach to Evaluating New Psychoactive Substances Activity and Mechanisms. Advanced Science May 1, 2025
- A Caenorhabditis elegans p38 MAP kinase pathway mutant protects from dopamine, methamphetamine, and MDMA toxicity. Neuroscience Letters July 1, 2011