Experimental anxiety-depressive state in rats caused by neonatal exposure to the inhibitor of dipeptidyl peptidase IV, diprotin A: effects of imipramine
Keywords:
experimental anxiety-depressive state; inhibitor of dipeptidyl peptidase-IV, diprotin A; rats; forced swimming test; imipramine; corticosterone.
Abstract
Previously, we have shown that the inhibitor of proline-specific peptidase, dipeptidyl peptidase-IV (DP-IV, EC 3.4.14.5), tripeptide diproptin A administered on postnatal days 5-18 induced emotional and motivational disorders in adolescent and adult rats. These disorders can be considered a model of a mixed anxiety-depression-like disorder. However, validation studies of this model are not available. The aim of this work was to test the effect of the tricyclic antidepressant, imipramine (IMI), on depressive-like behavior in rats and the level of serum corticosterone using the model of mixed anxiety-depressive state. Methods. The level of anxiety was assessed by the automated Elevated Plus Maze test and the depressive-like behavior was evaluated by the forced swimming test in one- and two-month old rats. IMI was administered to adult animals for ten days (20 mg/kg a day, intragastrically). Serum corticosterone concentrations were measured using ELISA. Results. The neonatal exposure to diprotin A increased anxiety in one-month old rats. The depressive-like behavior was observed in animals aged one and two months. IMI normalized behavior of animals in the forced swimming test and reduced serum levels of corticosterone. Also, IMI reduced body weight of rats. Conclusion. The results of the study evidenced adequacy of the model of mixed anxiety-depressive state induced by the DP-IV inhibitor, diprotin A, on the second and third postnatal weeks to the clinical prototype of disease according to criteria of face validity, predictive and construct validity.
Downloads
Download data is not yet available.
References
1. Hochberg Z., Feil R., Constancia M., Fraga M., Junien C., Carel J.-C. et al. Child Health, Developmental Plasticity, and Epigenetic Programming. Endocr. Rev. 2011. 32(2): 159-224. doi: 10.1210/er.2009-0039
2. Gershon A., Sudheimer K., Tirouvanziam R., Williams L.M., O’Hara R. The long-term impact of early adversity on late-life psychiatric disorders. Curr. Psychiatry Rep. 2013; 15(4): 352. doi: 10.1007/s11920-013-0352-9
3. Poletaeva I.I., Perepelkina O.V., Boiarshinova O.S., Lil’p I.G., Markina N.V., Timoshenko T.V. et al. Neonatal injections of pharmacological agents and their remote genotype-dependent effects in mice and rats. Ontogenez. 2012; 43(6): 387-400. (in Russian)
4. van Bodegom M., Homberg J.R., Henckens M.J.A.G. Modulation of the hypothalamic-pituitary-adrenal axis by early life stress exposure. Front. Cell Neurosci. 2017; 11: 87. doi: 10.3389/fncel.2017.00087
5. Deng J., Lamb J.R., McKeown A.P., Miller S., Muglia P., Guest P.C. et al. Identification of altered dipeptidyl-peptidase activities as potential biomarkers for unipolar depression. J. Affect. Disord. 2013;151(2): 667-72. doi: 10.1016/j.jad.2013.07.015.
6. Neznamov G.G., Zolotov N.N., Syunyakov T.S., Syunyakov S.A., Metlina M.V., Nazarova G.A. Activity of prolyn-specific enzymes in patients with anxiety disorders and its changes during Afobazole treatment. Psihiatrija i psihofarmakoterapija. 2014; 16(1): 21-7. (in Russian)
7. Frerker N., Raber K., Bode F., Skripuletz T., Nave H., Klemann C. et al. Phenotyping of congenic dipeptidyl peptidase 4 (DP4) deficient Dark Agouti (DA) rats suggests involvement of DP4 in neuro-, endocrine, and immune functions. Clin. Chem. Lab Med. 2009; 47(3): 275-87. doi: 10.1515/CCLM.2009.064
8. Krupina N.A., Kushnareva E.Iu., Khlebnikova N.N., Zolotov N.N., Kryzhanovskii G.N. Experimental model of anxiety-depression state in rats exposed to inhibitor of dipeptidyl peptidase IV methionyl-2(S)-cyano-pyrrolidine in early postnatal period. Zh. Vyssh Nerv Deiat Im I P Pavlova. 2009; 59(3): 360-372. (in Russian)
9. Khlebnikova N.N., Kushnareva E.Yu., Krupina N.A., Rodina V.I. Novel synthetic inhibitor of dipeptidyl peptidase IV methionyl-2(S)-cyanopyrrolidine induces latent aggression in rats. Eur. Neuropsychopharmacol. 2011; 21(Suppl.3): S302. doi: http://dx.doi.org/10.1016/S0924-977X(11)70477-1
10. Krupina N.A., Khlebnikova N.N. 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. doi: 10.4236/jbbs.2016.64018.
11. Khlebnikova N.N., Krupina N.A., Kushnareva E.Yu., Zolotov N.N., Kryzhanovskii G.N. 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): 409-12. doi: 10.1007/s10517-012-1540-z
12. Krupina N.A., Zubkov E.A., Orshanskaya E.V., Zorkina Y.A., Khlebnikova N.N. Gene expression in the brain of adult rats with behavioural alterations caused by neonatal exposure to the dipeptidyl peptidase-IV inhibitors diprotin A and sitagliptin. Eur. Neuropsychopharmacol. 2016; 26(Suppl. 2): S173. doi: 10.1016/S0924-977X(16)31000-8
13. Khlebnikova N.N., Krupina N.A., Kushnareva E.Y. Blood serum corticosterone level in modeling depression-like states in rats. Patol. Fiziol. Eksp. Ter. 2013; 4:3-9. (in Russian).
14. Belzung C., Lemoine M. Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression. Biol. Mood Anxiety Disord. 2011; 1(1):9. doi: 10.1186/2045-5380-1-9.
15. Walf A.A., Frye Ch.A. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols. 2007; 2: 322-28. http://dx.doi.org/10.1038/nprot.2007.44.
16. O’Leary, T.P., Gunn, R.K. and Brown, R.E. What are we measuring when we test strain differences in anxiety in mice? Behavior Genetics. 2013; 43: 34-50. http://dx.doi.org/10.1007/s10519-012-9572-8.
17. Porsolt R.D., Anton G., Blavet N., Jalfre M. Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur. J. Pharmacol. 1978; 47 (4): 379 — 91.
18. Overstreet D.H., Pucilowski O., Rezvani A.H., Janowsky D.S. Administration of antidepressants, diazepam and psychomotor stimulants further confirms the utility of Flinders Sensitive Line rats as an animal model of depression. Psychopharmacology (Berl). 1995;121(1): 27-37.
19. Wang Q., Timberlake M.A. Prall K., Dwivedi Y. The recent progress in animal models of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2017; 77: 99-109. doi: 10.1016/j.pnpbp.2017.04.008.
20. Mogensen J., Pedersen T.K., Holm S. Effects of chronic imipramine on exploration, locomotion, and food/water intake in rats. Pharmacol Biochem Behav. 1994; 47(3): 427-35. https://doi.org/10.1016/0091-3057(94)90139-2
21. Kasyanov E.D., Mazo G.E. The hypothalamic-pituitary-adrenal axis functioning in depressive disorder: current state of the problem. Psihicheskoe zdorov’e. 2017. 8: 27-34. (in Russian)
22. Anacker C., O’Donnell K.J., Meaney M.J. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function. Dialogues Clin. Neurosci. 2014; 16(3): 321-33.
23. Frost P., Bornstein S., Ehrhart-Bornstein M., O’Kirwan F. Hutson C., Heber D. et al. The prototypic antidepressant drug, imipramine, but not Hypericum perforatum (St. John’s Wort), reduces HPA-axis function in the rat. Horm. Metab. Res. 2003; 35(10): 602-06. doi: 10.1055/s-2003-43507
24. Klemann C., Wagner L., Stephan M., von Hоrsten S. Cut to the chase: a review of CD26/dipeptidyl peptidase-4’s (DPP4) entanglement in the immune system. Clin. Exp. Immunol. 2016; 185(1): 1-21, doi: 10.1111/cei.12781
25. Mentlein R. Cell-surface peptidases. Int. Rev. Cytol. 2004; 235: 165-213.
26. Raison C.L., Capuron L., Miller A.H. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006; 27(1): 24-31. doi: 10.1016/j.it.2005.11.006
27. Oglodek E., Szota A., Just M., Mos D., Araszkiewicz A. The role of the neuroendocrine and immune systems in the pathogenesis of depression. Pharmacol. Rep. 2014; 66(5): 776-81. doi: 10.1016/j.pharep.2014.04.009.
28. Maletic V., Robinson M., Oakes T., Iyengar S., Ball S.G., Russell J. Neurobiology of depression: an integrated view of key findings. Clin. Pract. 2007; 61(12): 2030-40. doi: 10.1111/j.1742-1241.2007.01602.x
29. Suzuki H., Savitz J., Kent Teague T., Gandhapudi S.K., Tan C., Misaki M. et al. Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance. Brain Behav. Immun. 2017; 66:193-200. doi: 10.1016/j.bbi.2017.06.011
30. Zhai X.J, Chen F, Chen C, Zhu C.R, Lu Y.N. LC-MS/MS based studies on the anti-depressant effect of hypericin in the chronic unpredictable mild stress rat model. J. Ethnopharmacol. 2015;169: 363-9. doi: 10.1016/j.jep.2015.04.053.
2. Gershon A., Sudheimer K., Tirouvanziam R., Williams L.M., O’Hara R. The long-term impact of early adversity on late-life psychiatric disorders. Curr. Psychiatry Rep. 2013; 15(4): 352. doi: 10.1007/s11920-013-0352-9
3. Poletaeva I.I., Perepelkina O.V., Boiarshinova O.S., Lil’p I.G., Markina N.V., Timoshenko T.V. et al. Neonatal injections of pharmacological agents and their remote genotype-dependent effects in mice and rats. Ontogenez. 2012; 43(6): 387-400. (in Russian)
4. van Bodegom M., Homberg J.R., Henckens M.J.A.G. Modulation of the hypothalamic-pituitary-adrenal axis by early life stress exposure. Front. Cell Neurosci. 2017; 11: 87. doi: 10.3389/fncel.2017.00087
5. Deng J., Lamb J.R., McKeown A.P., Miller S., Muglia P., Guest P.C. et al. Identification of altered dipeptidyl-peptidase activities as potential biomarkers for unipolar depression. J. Affect. Disord. 2013;151(2): 667-72. doi: 10.1016/j.jad.2013.07.015.
6. Neznamov G.G., Zolotov N.N., Syunyakov T.S., Syunyakov S.A., Metlina M.V., Nazarova G.A. Activity of prolyn-specific enzymes in patients with anxiety disorders and its changes during Afobazole treatment. Psihiatrija i psihofarmakoterapija. 2014; 16(1): 21-7. (in Russian)
7. Frerker N., Raber K., Bode F., Skripuletz T., Nave H., Klemann C. et al. Phenotyping of congenic dipeptidyl peptidase 4 (DP4) deficient Dark Agouti (DA) rats suggests involvement of DP4 in neuro-, endocrine, and immune functions. Clin. Chem. Lab Med. 2009; 47(3): 275-87. doi: 10.1515/CCLM.2009.064
8. Krupina N.A., Kushnareva E.Iu., Khlebnikova N.N., Zolotov N.N., Kryzhanovskii G.N. Experimental model of anxiety-depression state in rats exposed to inhibitor of dipeptidyl peptidase IV methionyl-2(S)-cyano-pyrrolidine in early postnatal period. Zh. Vyssh Nerv Deiat Im I P Pavlova. 2009; 59(3): 360-372. (in Russian)
9. Khlebnikova N.N., Kushnareva E.Yu., Krupina N.A., Rodina V.I. Novel synthetic inhibitor of dipeptidyl peptidase IV methionyl-2(S)-cyanopyrrolidine induces latent aggression in rats. Eur. Neuropsychopharmacol. 2011; 21(Suppl.3): S302. doi: http://dx.doi.org/10.1016/S0924-977X(11)70477-1
10. Krupina N.A., Khlebnikova N.N. 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. doi: 10.4236/jbbs.2016.64018.
11. Khlebnikova N.N., Krupina N.A., Kushnareva E.Yu., Zolotov N.N., Kryzhanovskii G.N. 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): 409-12. doi: 10.1007/s10517-012-1540-z
12. Krupina N.A., Zubkov E.A., Orshanskaya E.V., Zorkina Y.A., Khlebnikova N.N. Gene expression in the brain of adult rats with behavioural alterations caused by neonatal exposure to the dipeptidyl peptidase-IV inhibitors diprotin A and sitagliptin. Eur. Neuropsychopharmacol. 2016; 26(Suppl. 2): S173. doi: 10.1016/S0924-977X(16)31000-8
13. Khlebnikova N.N., Krupina N.A., Kushnareva E.Y. Blood serum corticosterone level in modeling depression-like states in rats. Patol. Fiziol. Eksp. Ter. 2013; 4:3-9. (in Russian).
14. Belzung C., Lemoine M. Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression. Biol. Mood Anxiety Disord. 2011; 1(1):9. doi: 10.1186/2045-5380-1-9.
15. Walf A.A., Frye Ch.A. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols. 2007; 2: 322-28. http://dx.doi.org/10.1038/nprot.2007.44.
16. O’Leary, T.P., Gunn, R.K. and Brown, R.E. What are we measuring when we test strain differences in anxiety in mice? Behavior Genetics. 2013; 43: 34-50. http://dx.doi.org/10.1007/s10519-012-9572-8.
17. Porsolt R.D., Anton G., Blavet N., Jalfre M. Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur. J. Pharmacol. 1978; 47 (4): 379 — 91.
18. Overstreet D.H., Pucilowski O., Rezvani A.H., Janowsky D.S. Administration of antidepressants, diazepam and psychomotor stimulants further confirms the utility of Flinders Sensitive Line rats as an animal model of depression. Psychopharmacology (Berl). 1995;121(1): 27-37.
19. Wang Q., Timberlake M.A. Prall K., Dwivedi Y. The recent progress in animal models of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2017; 77: 99-109. doi: 10.1016/j.pnpbp.2017.04.008.
20. Mogensen J., Pedersen T.K., Holm S. Effects of chronic imipramine on exploration, locomotion, and food/water intake in rats. Pharmacol Biochem Behav. 1994; 47(3): 427-35. https://doi.org/10.1016/0091-3057(94)90139-2
21. Kasyanov E.D., Mazo G.E. The hypothalamic-pituitary-adrenal axis functioning in depressive disorder: current state of the problem. Psihicheskoe zdorov’e. 2017. 8: 27-34. (in Russian)
22. Anacker C., O’Donnell K.J., Meaney M.J. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function. Dialogues Clin. Neurosci. 2014; 16(3): 321-33.
23. Frost P., Bornstein S., Ehrhart-Bornstein M., O’Kirwan F. Hutson C., Heber D. et al. The prototypic antidepressant drug, imipramine, but not Hypericum perforatum (St. John’s Wort), reduces HPA-axis function in the rat. Horm. Metab. Res. 2003; 35(10): 602-06. doi: 10.1055/s-2003-43507
24. Klemann C., Wagner L., Stephan M., von Hоrsten S. Cut to the chase: a review of CD26/dipeptidyl peptidase-4’s (DPP4) entanglement in the immune system. Clin. Exp. Immunol. 2016; 185(1): 1-21, doi: 10.1111/cei.12781
25. Mentlein R. Cell-surface peptidases. Int. Rev. Cytol. 2004; 235: 165-213.
26. Raison C.L., Capuron L., Miller A.H. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006; 27(1): 24-31. doi: 10.1016/j.it.2005.11.006
27. Oglodek E., Szota A., Just M., Mos D., Araszkiewicz A. The role of the neuroendocrine and immune systems in the pathogenesis of depression. Pharmacol. Rep. 2014; 66(5): 776-81. doi: 10.1016/j.pharep.2014.04.009.
28. Maletic V., Robinson M., Oakes T., Iyengar S., Ball S.G., Russell J. Neurobiology of depression: an integrated view of key findings. Clin. Pract. 2007; 61(12): 2030-40. doi: 10.1111/j.1742-1241.2007.01602.x
29. Suzuki H., Savitz J., Kent Teague T., Gandhapudi S.K., Tan C., Misaki M. et al. Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance. Brain Behav. Immun. 2017; 66:193-200. doi: 10.1016/j.bbi.2017.06.011
30. Zhai X.J, Chen F, Chen C, Zhu C.R, Lu Y.N. LC-MS/MS based studies on the anti-depressant effect of hypericin in the chronic unpredictable mild stress rat model. J. Ethnopharmacol. 2015;169: 363-9. doi: 10.1016/j.jep.2015.04.053.
Published
2017-12-18
How to Cite
Khlebnikova N. N., Krupina N. A. Experimental anxiety-depressive state in rats caused by neonatal exposure to the inhibitor of dipeptidyl peptidase IV, diprotin A: effects of imipramine // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2017. VOL. 61. № 4. PP. 4–12.
Issue
Section
Original research
