Two Metabolites of [Leu]enkephalin, Tyr-Gly and Tyr-Gly-Gly-Phe, Impair Acquisition of an Active Avoidance Response in Mice

Abstract

Two tyrosine-containing enkephalin metabolites, Tyr-Gly and Tyr-Gly-Gly-Phe, were found to impair acquisition of a one-way active avoidance response when administered intraperitoneally to mice. Prior studies demonstrated that the enkephalin metabolite Tyr-Gly-Gly also impairs avoidance acquisition, but that the tetrapeptide Gly-Gly-Phe-Leu is without similar effects. Since [leu]enkephalin also impairs acquisition of the avoidance response, these data are consistent with the suggestion that enkephalin metabolites containing an N-terminal tyrosine may be the active principals for the behavioral effects produced by [leu]enkephalin. Alternatively, these metabolites may represent a separate class of pharmacological agents that shares some behavioral effects with the enkephalins, but that produces effects on learning through a different mechanism.