A New Model of Morphine-Induces Emesis in Suncus murinus (House Musk Shrew)
Refereed conference paper presented and published in conference proceedings
CUHK Authors
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AbstractIntroduction Opioids represent the most potent analgesic drugs, but they have several limiting side effects, including nausea and emesis. The house musk shrew, Suncus murinus, was introduced as an experimental model for emesis research in 1987. However, previous studies concluded that morphine does not induce emesis in this species. It is possible that previous studies missed its emetic potential because the doses used were outside of its anticipated narrow ‘bell-shaped’ response profile [1]. In the present studies, we carefully evaluated the action of morphine focussing particularly around 0.3 mg/kg and recorded behavioural and physiological changes for up to 24 h. Method Male Suncus murinus (n = 3-6) were implanted with radiotelemetry devices. One week later, they were injected with morphine (0.01-10 mg/kg, s.c.) or vehicle (0.9% NaCl, 2ml/kg, s.c.) and placed into whole-body plethysmography chambers to record behaviour and respiratory function with gastric myoelectric activity (GMA) and temperature using radiotelemetry simultaneously [2]. In other studies, isolated intestinal segments were subjected to electrical field stimulation (EFS) to characterize the potency of morphine at opioid receptors. Results The behavioural tests showed subcutaneous injection of morphine induced retching and emesis, with a bell-shaped dose-response curve; the optimal dose was 0.3 mg/kg. In contrast, morphine dose-dependently increased food intake and body temperature. Morphine (0.3-3 mg/kg) increased the dominant frequency (DF) of slow waves but did not change the percentage power of bradygastria, normogastria, or tachygastria. None of the doses of morphine affected respiratory function (Table 1). The organ bath studies showed morphine inhibited EFS-induced contraction of isolated ileum and distal colon (ileum, pEC₅₀ = 6.29; distal colon, pEC₅₀ = 5.61). The action of morphine on the isolated tissues was antagonised by the opioid receptor antagonist, naloxone. Conclusion The studies reveal that morphine induces retching and emesis in Suncus murinus and causes behavioural modification and physiological changes. The in vitro studies provide evidence that morphine active opioid receptors to modulate neuroeffector mechanisms in the gastrointestinal. References [1] S. Kakimoto, H. Saito, N. Matsuki, Antiemetic Effects of Morphine on Motion- and Drug-Induced Emesis in Suncus murinus, Biological and Pharmaceutical Bulletin 20 (1997) 739-742. [2] L.L. Tu, Z.B. Lu, K. Dieser, C. Schmitt, S.W. Chan, M.P. Ngan, P.L.R. Andrews, E. Nalivaiko, J.A. Rudd, Brain Activation by H-1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in Suncus murinus (House Musk Shrew), Front Physiol 8 (2017).
All Author(s) ListChung Man Jessical HUI, Peng DU, Yuen Hang Julia LIU, Luping LIU, Zengbing LU, Lingqing YANG, Aleena Khalid, Heidi S.H. NG, Zitong LI, Dexuan CUI, Bin JIANG, Yingyi DENG, Man Piu NGAN, John RUDD
Name of Conference19th World Congress of Basic & Clinical Pharmacology 2023
Start Date of Conference02/07/2023
End Date of Conference07/07/2023
Place of ConferenceGlasgow, Scotland
Country/Region of ConferenceGreat Britain
Year2023
Month7
Day5
LanguagesEnglish-United Kingdom