| pA2 online © Copyright 2004 The British Pharmacological Society |
009P
University of Newcastle Winter Meeting December 2004 |
Attenuation of the gerbil writhing response by Elizabeth L. Gallantine1,2, Farhad Kamali1 and Theo F. Meert2.1 School of Clinical & Laboratory Sciences, University of Newcastle, Newcastle upon Tyne, UK. 2CNS Discovery Research, Johnson & Johnson PRD, Beerse, Belgium. |
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– opioids, and neurokinin -1, -2, and -3 antagonists
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-opioid receptor agonists are reported to attenuate the acetic acid - induced abdominal constriction response in mice (Sora et al., 1999). Neurokinin-1 (NK-1), -2 and –3 receptor antagonists also display activity in several visceral pain models (Nagahisa et al. 1992; Mclean et al.,1998; Julia et al., 1999). As the gerbil NK-1 receptor is comparable to the human receptor, we evaluated the efficacy of NK-1, -2 and –3 receptor antagonists and opioids (both alone and in combination) in the writhing test in this species. Adult female gerbils (Meriones unguiculatus, Crl(MON)BR; Charles River, Sulzfeld, Germany) weighing 50-60g received subcutaneous injections of either the μ-opioids morphine or fentanyl, the -opioid U50,488-H, the -opioid SNC80, NK-1 antagonists R116301, CP-96,345 or GR203040, the NK-2 antagonist SR-48968 or the NK-3 antagonist SR-142801. Writhing was evoked 1 hour after treatment by intraperitoneal injection of 0.2ml 1% acetic acid solution and the frequency of the response was recorded.
Morphine, fentanyl and U50,488-H significantly (P <0.001) attenuated the writhing response dose-dependently with complete inhibition occurring at the highest doses. SNC80 did not significantly attenuate the writhing response not even at a dose of 40 mg/kg. The tachykinin NK-1 antagonists CP-96,345 and GR203040, the NK-2 antagonist SR-48968 and the NK-3 antagonist SR-142801 significantly reduced (P <0.01) the writhing frequency without complete inhibition (see Gallantine & Meert 2004). The NK-1 antagonist R116301 displayed only limited activity at doses up to 40 mg/kg. Co-administration of an NK-1, -2 or –3 antagonist with an opioid did not potentiate the opioid efficacy. Selective NK antagonists may therefore be effective in a visceral nociception assay in gerbils but do not appear to modulate opioid action within this model.
Gallantine EL & Meert TF. Pharmacology Biochemistry and Behavior 79 (2004) 125 –135.
Julia V et al., Gastroenterology 116 (1999) 1124-1131.
Mclean PG et al., European Journal of Pharmacology 345 (1998) 247-252.
Nagahisa A et al., European Journal of Pharmacology 217 (1992) 191-195.
Sora I et al., European Journal of Pharmacology 366 (1999) R3-R5.