Dipeptidyl Peptidase 4 Inhibitors Diprotin A and Sitagliptin Administered on Weeks 2-3 of Postnatal Development Modulate Monoamine Metabolism in the Striatum of Adult Rats.

The levels of monoamines and their metabolites in brain structures of adult (3-month-old) rats with emotional and motivational disorders induced by inhibitors of dipeptidyl peptidase 4 (DPP-4; EC 3.4.14.5) diprotin A and sitagliptin on weeks 2-3 of postnatal development (postnatal days 5-18) were studied by HPLC with electrochemical detection. A significant decrease in the level of serotonin metabolite, 5-hydroxyindoleacetic acid, and a pronounced tendency towards reduced serotonin level were detected in the striatum of rats in both study groups. In adult rats treated with diprotin A during the neonatal period, a tendency towards activation of dopamine metabolism was observed (judging from DOPAC/DA ratio). The levels of monoamines and their metabolites in the frontal cortex, hypothalamus, and amygdala remained unchanged. The findings suggest that administration of DPP-4 inhibitors during the neonatal period induces long-term dysfunction of the serotonergic and dopaminergic systems of the brain.