Hyperactivity versus explosive motor behavior induced by opioids in the rat. Mechanisms elucidated with enkephalin-tyrosine-o-sulfate and morphine congeners

Abstract

A relatively mild hyperactive state (HAS), characterized by agitation and hypermotility, is induced by opiate drugs and opioid peptides in general and is blocked by naloxone. HAS can be distinguished from the profound hyperresponsiveness of an explosive motor behavior (EMB). Sulfation of the phenolic moiety in morphine or in methionine enkephalin essentially abolishes opiate receptor binding activity. The sulfated peptide lacks detectable pharmacological activity in the rat, whereas sulfated morphine is several hundred-fold more potent than morphine in eliciting (EMB). Thus, EMB is elicited only by congeners of morphine having appropriate hydrophilic substitution at C-6 and which is mediated through a receptor that is insensitive to naloxone.