Effect of imipramine and prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on activity of proline-specific peptidases in the brain of rats with experimental anxious-depressive syndrome.

Activities of prolyl endopeptidase and dipeptidyl peptidase IV in the frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocampus were measured in rats with the experimental anxious-depressive syndrome induced by treatment with a dipeptidyl peptidase IV inhibitor during the early postnatal period (days 5-18). Prolyl endopeptidase activity was elevated in the frontal cortex, hypothalamus, and nucleus accumbens. Increased activity of dipeptidyl peptidase IV was observed in the hypothalamus and striatum. Norepinephrine/serotonin reuptake inhibitor, imipramine, and noncompetitive prolyl endopeptidase inhibitor, benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine, were shown to abolish depression-like behavior of animals in the forced swimming test. These compounds had a normalizing effect on activities of prolyl endopeptidase and dipeptidyl peptidase IV in brain structures of rats.