Frerker, N., Raber, K., Bode, F., Skripuletz, T., Nave, H., Klemann, C., Pabst, R., Stephan, M., Schade, J., Brabant, G., Wedekind, D., Jacobs, R., Jorns, A., Forssmann, U., Straub, R.H., Johannes, S., Hoffmann, T., Wagner, L., Demuth, H.U. and von Horsten, S. (2009) Phenotyping of Congenic Dipeptidyl Peptidase 4 (DP4) Deficient Dark Agouti (DA) Rats Suggests Involvement of DP4 in Neuro-, Endocrine, and Immune Functions. Clinical Chemistry and Laboratory Medicine, 47, 275-287.
http://dx.doi.org/10.1515/CCLM.2009.064

has been cited by the following article:

• TITLE: Neonatal Exposure to the Dipeptidyl Peptidase-IV Inhibitors Diprotin A and Sitagliptin Induces Depression-Like Behavior, Anxiety, and Latent Aggression in Adolescent and Adult Rats

  AUTHORS: Nataliya A. Krupina, Nadezhda N. Khlebnikova

  KEYWORDS: Dipeptidyl Peptidase IV Inhibitors, Rat, Depression, Anxiety, Aggression

  JOURNAL NAME: Journal of Behavioral and Brain Science, Vol.6 No.4, April 15, 2016

  ABSTRACT: Emotional and motivational disorders in adults are often considered to be the result of altered neurodevelopment. Clinical and experimental data provide evidence that serine protease dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) is involved in the pathophysiology of psycho-emotional disorders. Recently, we have shown that adolescent and adult rats exhibit an increase in anxiety and depression-related behaviors after neonatal administration of a synthetic non-competitive inhibitor of DPP-IV, methionyl-2(S)-cyano-pyrrolidine. In the present study, we tested the effects of two competitive, selective DPP-IV inhibitors, sitagliptin (4 mg/kg) and diprotin A (2 mg/kg), administered at postnatal days 5 - 18 on the emotional and motivational behavior of adolescent and adult rats. We observed increased anxiety in one-month-old diprotin A- or sitagliptin-treated rats in the elevated plus maze; diprotin A also enhanced the animals’ anxiety score using a ranked scale for evaluating anxiety and phobias. In the sucrose consumption and preference test, depressive-like behavior was pronounced in both the diprotin A- and sitagliptin-treated one-month-old animals, while only the diprotin A-treated rats exhibited a decrease in sucrose consumption at the age of 2 months. The diprotin A-treated rats also demonstrated behavioral despair and decreased activity in the forced swimming test within 1 - 3 months of age. Increased aggression was observed in 1 - 3-month-old diprotin A-treated rats and in two-month-old sitagliptin-treated rats. These findings support the hypothesis that DPP-IV is involved in the genesis of emotional and motivational disorders. Additionally, the results show that diprotin А impairs the adolescent and adult rats’ behavior more significantly than sitagliptin when the animals were treated with the DPP-IV inhibitors in the early postnatal period.