Differential sensitivity of models of antinociception in the rat, mouse and guinea‐pig to μ‐and κ‐opioid receptor agonists

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Abstract
A range of opioid receptor agonists were tested for activity in five antinociceptive models: the acetylcholine-induced abdominal constriction, tail-flick and hot plate tests in the mouse and the paw pressure test in the rat and guinea-pig. Agonists acting preferentially as the .kappa.-opioid receptor were significantly more potent in the guinea-pig than in the rat paw pressure test, whereas .mu.-receptor preferring agonists were equipotent in the two tests. The mouse abdominal constriction test was of equal sensitivity to the guinea-pig pressure test for both types of agonist. The mouse tail-flick and hot plate tests were progressively less sensitive than the other three tests, particularly to .kappa.-receptor preferring agonists. The efficacy of an agonist can also markedly affect its activity in antinociceptive tests. Thus, partial .kappa.-agonists were weak or inactive in the rat paw pressure test, and partial agonists at both .mu.- and .kappa.-opioid receptors were relatively weak in the tests in which heat was the noxious stimulus, particularly the mouse hot plate test. The mouse abdominal constriction test is suggested as the most appropriate antinociceptive model for testing a broad range of opioid agonists, whilst the relative potency of a drug in the rat and guinea-pig paw pressure tests may indicate the degree to which it is selective for .kappa.-opioid receptors in vivo.