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• W3138185846 abstract "An opioid epidemic is spreading in North America with millions of opioid overdoses annually. Opioid drugs, like fentanyl, target the mu opioid receptor system and induce potentially lethal respiratory depression. The challenge in opioid research is to find a safe pain therapy with analgesic properties but no respiratory depression. Current discoveries are limited by lack of amenable animal models to screen candidate drugs. Zebrafish (Danio rerio) is an emerging animal model with high reproduction and fast development, which shares remarkable similarity in their physiology and genome to mammals. However, it is unknown whether zebrafish possesses similar opioid system, respiratory and analgesic responses to opioids than mammals. In freely-behaving larval zebrafish, fentanyl depresses the rate of respiratory mandible movements and induces analgesia, effects reversed by μ-opioid receptor antagonists. Zebrafish presents evolutionary conserved mechanisms of action of opioid drugs, also found in mammals, and constitute amenable models for phenotype-based drug discovery.When it comes to treating severe pain, a doctor’s arsenal is somewhat limited: synthetic or natural opioids such as morphine, fentanyl or oxycodone are often one of the only options available to relieve patients. Yet these compounds can make breathing slower and shallower, quickly depriving the body of oxygen and causing death. This lethal side-effect is particularly devastating as opioids misuse has reached dangerously high levels in the United States, creating an ‘opioid epidemic’ which has claimed the lives of over 80,000 Americans in 2020. It is therefore crucial to find safer drugs that do not have this effect on breathing, but this research has been slowed down by the lack of animal models in which to study the effect of new compounds. Zebrafish are small freshwater fish that reproduce and develop fast, yet they are also remarkably genetically similar to mammals and feature a complex nervous system. However, it is not known whether the effect of opioids on zebrafish is comparable to mammals, and therefore whether these animals can be used to test new drugs for pain relief. To investigate this question, Zaig et al. exposed zebrafish larvae to fentanyl, showing that the fish then exhibited slower lower jaw movements – a sign of decreased breathing. The fish also could also tolerate a painful stimulus for longer, suggesting that this opioid does reduce pain in the animals. Together, these results point towards zebrafish and mammals sharing similar opioid responses, demonstrating that the fish could be used to test potential pain medications. The methods Zaig et al. have developed to establish these results could be harnessed to quickly assess large numbers of drug compounds, as well as decipher how pain emerges and can be stopped." @default.
• W3138185846 created "2021-03-29" @default.
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• W3138185846 date "2021-03-15" @default.
• W3138185846 modified "2023-09-23" @default.
• W3138185846 title "Respiratory depression and analgesia by opioid drugs in freely behaving larval zebrafish" @default.
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• W3138185846 doi "https://doi.org/10.7554/elife.63407" @default.
• W3138185846 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8060028" @default.
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