Experience-dependent regulation of Leu-enkephalin hydrolysis in rat plasma.

We examined experience-dependent alterations in the production of individual enkephalin metabolites during Leu-enkephalin hydrolysis in rat plasma in vitro. High performance liquid chromatography separation and electrochemical detection were used to quantify accumulation of the primary N-terminal products of enkephalin hydrolysis, Tyr and Tyr-Gly-Gly. Blood was sampled from rats through indwelling femoral artery catheters before, during, and after active avoidance training or appropriate control treatments. Avoidance training increased Tyr production, as did handling and exposing animals to the novel avoidance chamber without foot-shock training. On the other hand, Tyr-Gly-Gly production was elevated by blood sampling alone, by handling/novelty, and by training, but the effect of training was significantly greater than the effects of either of the other treatments. Interestingly, Tyr-Gly-Gly production was highly correlated (r = -0.885) with a measure of escape performance. Since the enzymes that participate in enkephalin hydrolysis act upon a number of peptides, regulation of enzyme activity may be one mechanism whereby an organism can modulate levels of circulating peptides in response to environmental experiences; this may contribute to the expression of appropriate behavioral responses to those environmental experiences.