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Addiction has become a profound societal problem worldwide, and few effective treatments are available. The nematode  Caenorhabditis elegans  ( C. elegans ) is an excellent invertebrate model to study neurobiological disease states.  C. elegans  reportedly developed a preference for cues that had previously been paired with addictive drugs, similar to place conditioning findings in rodents. Moreover, several recent studies discovered and reported the existence of an opioid-like system in  C. elegans . Still unclear, however, is whether  C. elegans  exhibits addictive-like behaviors for opioids, such as morphine. In the present study, we found that  C. elegans  exhibited dose-dependent preference for morphine using the conditioned chemosensory-cue preference (CCP) test. This preference was blocked by co-treatment with the opioid receptor antagonist naloxone.  C. elegans  also exhibited aversion to naloxone-precipitated withdrawal from chronic morphine exposure. The expression of morphine-induced CCP and morphine withdrawal were abolished in worms that lacked the opioid-like receptor NPR-17. Dopamine-deficient mutant ( cat-2 (e1112) ) worms also did not exhibit morphine-induced CCP. These results indicate that the addictive function of the opioid system exists in  C. elegans , which may serve as a useful model of opioid addiction.

Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17