MK-801 blocks dynorphin A (1-13)-induced loss of the tail-flick reflex in the rat.
Dynorphin A (1-13) administered intrathecally to rats results in a dose-dependent loss of the tail-flick reflex. This effect is mediated, at least in part, by N-methyl-D-aspartate receptors. We examined the influence of pretreatment or post-treatment with MK-801 on this behavioral response. MK-801 administered i.p. 30 min prior to dynorphin provided dose-dependent protection against loss of the tail-flick reflex with an ED50 of 0.06 mg/kg. MK-801 administered after dynorphin had a dose- and time-dependent protective action. The dose of 0.06 mg/kg protected 63% of the animals from loss of the tail-flick reflex when injected 15 min after dynorphin. In contrast, 3 mg/kg did not protect animals when injected 15 min after dynorphin, but did protect 50% of the animals when injected 30 min post-dynorphin. Although we cannot exclude other effects mediated by MK-801, these data support our previous findings that dynorphin-induced loss of the tail-flick reflex involves the N-methyl-D-aspartate-receptor complex and support the contention that the process(es) initiated by dynorphin injection proceed rapidly (minutes rather than hours).
Isaac
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L
Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
Van Zandt O'Malley
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T
Ristic
H
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Stewart
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P
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004399:Dynorphins / Q000494:pharmacology*; D006358:Hot Temperature; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D012018:Reflex / Q000187:drug effects*; D013623:Tail
D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; C026843:dynorphin (1-13); D004399:Dynorphins