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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Krupina NA, Kryzhanovsky GN. Insufficiency of nigrostrital dopaminergic system as a of dopamine-dependent depression syndrome. Zh. Nevrol. Psikhiatr. 2003;103(4):42-47. Russian.
Krupina NA, Kushnareva EY, Khlebnikova NN, Zolotov NN, Kryzhanovskii GN. Experimental model of anxiety-depressive state in rats caused by administration of dipeptidyl peptidase IV inhibitor methionyl-2(S)-cyano-pyrrolidine during the early postnatal period. Zh. Vyssh. Nervn. Deyat. 2009;59(3):360-372. Russian.
Krupina NA, Khlebnikova NN, Orlova IN, Popkova EV, Rodina VI, Kryzhanovsky GN. Effects of chronic mild stress in Wistar and August rats: behavior and monoamine content in the striatum. Patogenez. 2012;10(2):50-58. Russian.
Kushnareva EY, Krupina NA, Khlebnikova NN, Kudrin VS, Zolotov NN, Kryzhanovskii GN. The levels of monoamines and their metabolites in the brain structures of rats with an experimental anxiodepressive state induced by administration of an inhibitor of dipeptidyl peptidase 4 in the early postnatal period. Neurochem. J. 2012;6(1):29-37.
Khlebnikova NN, Krupina NA, Kushnareva EY, Zolotov NN, Kryzhanovskii GN. 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. Bull. Exp. Biol. Med. 2012;152(4):409-412.
Khlebnikova NN, Kushnareva EYu, Kudrin VS, Krupina NA. The effects of imipramine and the inhibitor of prolylendopeptidase benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on the levels of monoamines and their metabolites in the brain of rats with an experimental anxious-depressive state. Neurochem. J. 2014;8(4):271-276.
Anstrom KK, Miczek KA, Budygin EA. Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats. Neuroscience. 2009;161(1):3-12.
Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Arlington, 2013.
Furuyashiki T, Deguchi Y. Roles of altered striatal function in major depression. Brain Nerve. 2012;64(8):919-926.
Hamon M, Blier P. Monoamine neurocircuitry in depression and strategies for new treatments. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2013;45:54-63.
Krupina NA, Khlebnikova NN. 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. J. Behav. Brain Sci. 2016;6(4):167-183.
Kulikov AV, Popova NK. Tryptophan hydroxylase 2 in seasonal affective disorder: underestimated perspectives? Rev. Neurosci. 2015;26(6):679-690.
Martin EI, Ressler KJ, Binder E, Nemeroff CB. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Psychiatr. Clin. North Am. 2009;32(4):549-575.
Shih JC, Chen K, Ridd MJ. Monoamine oxidase: From genes to behavior. Annu. Rev. Neurosci. 1999;22:197-217.
Yanowitch R, Coccaro EF. The neurochemistry of human aggression. Advances in Genetics. Huber R, Bannasch DL, Brennan P, eds. San Diego, 2011. Vol. 75, Ch. 7. P. 151-169.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 163, No. 2, pp. 150-155, February, 2017
Rights and permissions
About this article
Cite this article
Khlebnikova, N.N., Orshanskaya, E.V., Narkevich, V.B. et al. 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. Bull Exp Biol Med 163, 190–194 (2017). https://doi.org/10.1007/s10517-017-3763-5
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-017-3763-5