Dipeptidyl peptidase IV inhibitors diprotin A and sitagliptin administered in the first postnatal week change the level of monoamines and their metabolites in the brain of adult rats

Abstract

In our previous studies, we have shown that rat pups exposed to dipeptidyl peptidase IV (DP-IV) inhibitors during postnatal days (PND) 5-18 or PND 1-7, in adulthood develops anxiety-depressive state with stress-induced aggression. Behavioral disorders in adult rats caused by the action of DP-IV inhibitors in the second — third postnatal weeks are accompanied by changes in monoamine metabolism in the striatum. The aim of this study was to estimate the levels of monoamines and their metabolites in brain structures of adult rats exposed to diprotin A and sitagliptin at PND 1-7. Methods. Diprotin A (2 mg/kg) or sitagliptin (4 mg/kg) was administered intraperitoneally to rats of the experimental group, and physiological saline — to the control animals. The levels of monoamines and their metabolites were measured by the HPLC/ED in the frontal cortex, striatum, amygdala, hippocampus and hypothalamus in 2,5-months-old animals. Results. We revealed a significant decrease in the level
of serotonin in the frontal cortex and norepinephrine in the striatum. In addition, diprotin A increased serotonin turnover in the frontal cortex and amygdala. Conclusion. The data suggest that the action of DP-IV inhibitors at PND 1-7 induces long-term dysfunction of monoaminergic systems of the rat’s brain.