MK-801 blocks dynorphin A (1–13)-induced loss of the tail-flick reflex in the rat

Abstract

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 of 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 ED 50 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).