Enkephalins and learning and memory: a review of evidence for a site of action outside the blood-brain barrier.

A series of studies indicate that enkephalins exert dramatic influences on learning and memory in rats and mice, when studied with conditioning tasks that are both negatively and positively motivated. Pharmacological analysis of these enkephalin actions on conditioning suggests that the [leu]enkephalin acts through a delta opioid receptor which is located outside the blood-brain barrier. Control studies indicate that enkephalins do not simply affect the performance of a conditioned response through actions on shock sensitivity or locomotor activity. Characterization of the peripheral enkephalin mechanism that affects behavior suggests an action through an enzymatic system that controls the concentrations of enkephalin present at its receptors in the periphery. This enzymatic mechanism is sensitive to experience, since its activity changes following conditioning, which suggests that it may be a regulatory mechanism for behavior.