The mouse grid-shock analgesia test: pharmacological characterization of latency to vocalization threshold as an index of antinociception.
Latency to vocalization and jump/flinch behaviors were scored as the nociceptive endpoints in mice in a grid-shock apparatus that delivered increasing shock levels through a grid floor. Morphine produced a dose-dependent increase in latency to vocalization and was equieffective at a 70- or 80-dB vocalization level. The jump/flinch behavior was not dose dependently modified by morphine. The mouse grid-shock procedure was pharmacologically characterized by using the 70-dB level endpoint. The antinociceptive potencies of the mu opioid receptor agonist analgesics, morphine, methadone, fentanyl, oxycodone, meperidine, etorphine and codeine, correlated well (R = .989) with their clinical doses. The mixed opioid agonist-antagonist, pentazocine, and the partial mu receptor opioid agonist, buprenorphine, were partially effective. The alpha-2 adrenergic agonists clonidine and flupirtine and the serotonergic 5-HT1B agonists 1-(m-trifluoromethyl)piperazine and anpirtoline, were all effective antinociceptives with potencies 20 times less to one-half that of morphine. The gamma-aminobutyric acid agonist 4,5,6,7-tetrahydroisoxazolo[5,4- c]pyridin-3(2H)-one was partially effective, whereas the gamma-aminobutyric acid uptake inhibitors SKF 100300A [N-(4,4-diphenyl-3-butenyl)-guvacine] and tiagabine were highly effective and 6 and 2 times less potent than morphine, respectively. The muscarinic agonists, oxotremorine and arecoline, and the cholinesterase inhibitor, physostigmine, were also antinociceptive, ranging from 7 times less to 100 times more potent than morphine. The nonsteroidal anti-inflammatory analgesic, aspirin, was inactive. The present studies show that the latency to a defined level of vocalization as the nociceptive endpoint provides a reliable, highly reproducible and high through-put test for antinociception in nonrestrained mice.
Pharmaceuticals Division, Novo Nordisk, Malov, Denmark.
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Swedberg
D000698:Analgesia; D000818:Animals; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D011930:Reaction Time; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D014828:Vocalization, Animal / Q000187:drug effects*
D009294:Narcotics; D018341:Receptors, Adrenergic, alpha-2; D018079:Receptors, GABA; D011985:Receptors, Serotonin; D009020:Morphine