[Emotional Motivational Disorders in Rats as a Result of Diprotin A and Sitagliptin Administration in the First...

The inhibitors of proline specific peptidase dipeptidyl peptidase-IV (DPP-IV, CD 26; EC 3.4.14.5) diprotin A (2 mg/kg) and sitagliptin (4 mg/kg) upon daily systemic exposure in rat pups on postnatal days 1-7 induced emotional and motivational disorders in one- and two-month-old rats. In adolescent rats, both the inhibitors produced a decreased locomotion in the automated open field test and an in- creased depression-like behavior in the Forced Swimming Test. At the same time, diprotin A increased sucrose consumption (a percent of the body weight) while sitagliptin decreased anxiety in the Elevated Plus Maze (EPM). In adult rats, diprotin A caused an increase in anxiety according to the reduced pref- erence for open arms of the maze and both the inhibitors decreased the percentage of rats entering open. arms in the EPM. Adult diprotin A-treated animals demonstrated increased aggression in social contact test. as compared to sitagliptin-treated rats. The one-and two-month-old animals in both experimental groups exhibited a decreased weight as compared to the controls. The results of the study show that diprotin A compared with sitagliptin negatively affects emotional and motivational behavior in adolescent and adult rats by increased number of indices increasing depression, anxiety, and aggression, while the main result of sitagliptin is increased depression when the animals were treated with the DPP-IV inhibitors in the first postnatal week. The findings support the hypothesis that DPPIV is involved in the genesis of emotional-motivational disorders.