[Leu]enkephalin and its metabolite, Tyr-Gly-Gly, impair active avoidance retention.

The current study examined the effects of [leu]enkephalin and its metabolite, Tyr-Gly-Gly, given immediately posttraining on active avoidance performance measured 24 h later. Initial experiments revealed that, in comparison to zero or one training trials, providing mice with two training trials significantly increased active avoidance performance measured 24 h later; this enabled us to examine the effects on retention of peptides administered immediately after the two training trials. It was found that Tyr-Gly-Gly (16 and 53 micrograms/kg) and [leu]enkephalin (30 and 100 micrograms/kg) administered in this fashion both significantly impaired retention; the dose-response functions for both peptides were U-shaped. Since the effects of enkephalins are most likely mediated by opioid delta-receptors, and Tyr-Gly-Gly has little or no activity at opioid receptors, the effects of the parent peptide(s) and metabolite are presumably pharmacologically distinct.