Abstract
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.
Highlights
IntroductionAddiction, including both substance use disorder (e.g., stimulants, opioids, and alcohol) and behavioral addiction (e.g., gaming and gambling), affects the mind, body, and social activities of the sufferer and has become a profound societal problem worldwide
Addiction, including both substance use disorder and behavioral addiction, affects the mind, body, and social activities of the sufferer and has become a profound societal problem worldwide
A conditioned chemosensory-cue preference (CCP) experiment was first conducted to determine whether C. elegans forms associations with chemosensory cues that are paired with morphine
Summary
Addiction, including both substance use disorder (e.g., stimulants, opioids, and alcohol) and behavioral addiction (e.g., gaming and gambling), affects the mind, body, and social activities of the sufferer and has become a profound societal problem worldwide. A better understanding of the neurobiological basis of addiction and the discovery of more effective treatments are needed. The development of animal models of drug reward and addiction, especially using rodent models, has provided much of our current understanding about the neuroscience of addiction (Kuhn et al, 2019), this is still not sufficient to solve the problem. It is thought to have major advantages as a model organism to study neurobiology and disease states (Hulme and Whitesides, 2011). C. elegans was proposed to be used to model aspects of drug addiction (Engleman et al, 2016).
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