Dynorphin-related peptides cause motor dysfunction in the rat through a non-opiate action.

We compared effects on motor function of four peptides belonging to the dynorphin family--dynorphin-(1-17) (DYN-(1-17], dynorphin-(1-13) (DYN-(1-13], dynorphin-(1-8) (DYN-(1-8] and alpha-neo-endorphin (alpha NE). After intrathecal administration, each of these peptides produced dose-related, flaccid, hindlimb paralysis, with the order of potency being DYN-(1-17) greater than DYN-(1-13) greater than alpha NE congruent to DYN-(1-8). This motor dysfunction was not reversed or blocked by the opiate receptor antagonist naloxone and was not produced by a variety of other kappa-selective agonists. However, paralysis was produced by des-Tyr-dynorphin (DYN-(2-17], which does not act at the opioid receptor. Taken together, the present studies show that dynorphin-related peptides, uniquely amongst opioids, produce motor dysfunction, an action which does not appear to be mediated by opioid receptors.