Dynorphin A and related peptides administered intrathecally in the rat: a search for putative kappa opiate receptor activity.

The intrathecal delivery of dynorphin A (1-17) and (1-13) induces, with rapid onset, a severe motor dysfunction characterized by flaccid extension of the hindlimbs and complete loss of muscle tone. This motor effect does not appear to be mediated via opiate receptors as high doses of naloxone neither block nor reverse motor dysfunction, and it is produced by dynorphin A fragments inactive at opiate receptors. At doses just below those which produce motor dysfunction, dynorphin A has no effect on nociceptive responses in the hot-plate, tail-flick and writhing tests. The selective, kappa opiate agonist, U50488H, produces a significant, dose-dependent inhibition of writhing, which is antagonized by pretreatment with naloxone, but has no effect on hot-plate and tail-flick latency. The kappa agent U50488H does not produce motor dysfunction with doses as high as 300 nmol/rat. It appears that the potent kappa opiate activity exhibited by dynorphin A in vitro may not reflect in vivo effects of dynorphin after intrathecal administration.