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A Novel Behavioral Fish Model of Nociception for Testing Analgesics
Instituto de Medicina Molecular (IMM), Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028, Portugal
Faculdade de Engenharia, Universidade do Porto, Porto, 4200-465, Portugal
Centre for Toxicology, The School of Pharmacy, University of London, London, WC1N 1AX, UK
Department of Biomedical Science, UPEI-AVC, Charlottetown, PE, C1A4P3, Canada
* Author to whom correspondence should be addressed.
Received: 2 March 2011; in revised form: 29 March 2011 / Accepted: 11 April 2011 / Published: 18 April 2011
(This article belongs to the Special Issue Opioids
Abstract: Pain is a major symptom in many medical conditions, and often interferes significantly with a person’s quality of life. Although a priority topic in medical research for many years, there are still few analgesic drugs approved for clinical use. One reason is the lack of appropriate animal models that faithfully represent relevant hallmarks associated with human pain. Here we propose zebrafish (Danio rerio) as a novel short-term behavioral model of nociception, and analyse its sensitivity and robustness. Firstly, we injected two different doses of acetic acid as the noxious stimulus. We studied individual locomotor responses of fish to a threshold level of nociception using two recording systems: a video tracking system and an electric biosensor (the MOBS system). We showed that an injection dose of 10% acetic acid resulted in a change in behavior that could be used to study nociception. Secondly, we validated our behavioral model by investigating the effect of the analgesic morphine. In time-course studies, first we looked at the dose-response relationship of morphine and then tested whether the effect of morphine could be modulated by naloxone, an opioid antagonist. Our results suggest that a change in behavioral responses of zebrafish to acetic acid is a reasonable model to test analgesics. The response scales with stimulus intensity, is attenuated by morphine, and the analgesic effect of morphine is blocked with naloxone. The change in behavior of zebrafish associated with the noxious stimulus can be monitored with an electric biosensor that measures changes in water impedance.
Keywords: morphine; fish; dose-response; zebrafish
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Correia, A.D.; Cunha, S.R.; Scholze, M.; Stevens, E.D. A Novel Behavioral Fish Model of Nociception for Testing Analgesics. Pharmaceuticals 2011, 4, 665-680.
Correia AD, Cunha SR, Scholze M, Stevens ED. A Novel Behavioral Fish Model of Nociception for Testing Analgesics. Pharmaceuticals. 2011; 4(4):665-680.
Correia, Ana D.; Cunha, Sérgio R.; Scholze, Martin; Stevens, E. Don. 2011. "A Novel Behavioral Fish Model of Nociception for Testing Analgesics." Pharmaceuticals 4, no. 4: 665-680.