The study of the antidepressant and actoprotective activity of a synthetic analog of the terminal region of neuropeptide Y
Keywords:antidepressants; actoprotectors; neuropeptide Y
Topicality. Neuropeptide Y (NPY), which is significantly widespread in the human body, is responsible for various physiological processes, in particular it is involved in the regulation of the emotional behavior, memory and metabolism. The modified short fragment of NPY proposed – NP9 nonapeptide for intranasal administration – shows certain biological properties of the native peptide, in particular the anxiolytic and antiamnesic action. The effect of NP9 on affective disorders of depressive nature and physical endurance remains unknown.
Aim. To study the antidepressant and actoprotective activity of NP9 in models of tail suspension, reserpine-induced depression, and forced weighted swimming.
Materials and methods. The antidepressant properties of NP9 were studied in the immobilization tail suspension test in mice and on a model of reserpine-induced depression with registration of the body temperature, ptosis, and behavior in the Porsolt forced swimming tests and the open field test. The actoprotective properties of NP9 were studied in the swimming test with a load (10 % of the weight of the animal).
Results and discussion. In the tail suspension test, NP9 significantly increased the latent time of the first immobilization compared to the indicators of intact animals (3.2 times) and the imipramine group (2.7 times). NP9 did not significantly affect the manifestations of reserpine-induced depression. These results indicate the weak antidepressant properties of NP9. Nonapeptide significantly increased the swimming time to exhaustion by 2.5 times, indicating actoprotective properties, according to which NP9 exceeded the reference drug Semax.
Conclusions. In the tail suspension test, nonapeptide NP9 exhibits dose-dependent antidepressant properties after the first administration, but this effect is practically not manifested in the rigid reserpine-induced model of depression. NP9 increases the physical endurance of animals in the forced weighted swimming test and is superior to the reference drug Semax by its effectiveness.
Reichmann, F., Holzer, P. (2015). Neuropeptide Y: A stressful review. Neuropeptides, 55, 99–109. doi: https://doi.org/10.1016/j.npep.2015.09.008.
Morales-Medina, J. C., Dumont, Y., Quirion, R. (2010). A possible role of neuropeptide Y in depression and stress. Brain Research, 1314, 194–205. doi:10.1016/j.brainres.2009.09.077.
Crespi, F. (2011). Influence of Neuropeptide Y and antidepressants upon cerebral monoamines involved in depression: An in vivo electrochemical study. Brain Research, 1407, 27–37. doi: 10.1016/j.brainres.2011.05.033.
Mathé, A. A., Husum, H., Khoury, A. E., Jiménez-Vasquez, P., Gruber, S. H. M., Wörtwein, G., Angelucci, F. (2007). Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role? Physiology & Behavior, 92 (1-2), 226–231. doi: 10.1016/j.physbeh.2007.05.016.
Brothers, S., Wahlestedt, C. (2010). Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO Molecular Medicine. 2 (11), 429–439. doi: 10.1002/emmm.201000100.
Pedragosa-Badia, X., Stichel, J., Beck-Sickinger, A. G. (2013). Neuropeptide Y receptors: how to get subtype selectivity. Frontiers in endocrinology, 4. doi: 10.3389/fendo.2013.00005.
Zagayko, A., Havrylov, I., Lytkin, D. (2019). The study of the effect of the low molecular analog of neuropeptide Y on behavioral reactions in rats. Clinical Pharmacy, 23 (4). 30–36. doi: 10.24959/cphj.19.1509.
Kienast, C., Gunga, H.-C., Steinach, M. (2019). Neuropeptide Y – Its role in human performance and extreme environments. REACH, 14–15, 100032. doi: 10.1016/j.reach.2019.100032.
Nair, A., Jacob, S. (2016). A simple practice guide for dose conversion between animals and human. Journal Of Basic And Clinical Pharmacy. 7 (2), 27. doi: 10.4103/0976-0105.177703.
Meredith, M., Salameh, T., Banks, W. (2015). Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases. AAPS J. 17 (4), 780–787. doi: 10.1208/s12248-015-9719-7.
Zhao, J., Jung, Y., Jang, C., Chun, K., Kwon, S., Lee, J. (2015). Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression. Scientific Reports, 5 (1). doi: https://doi.org/10.1038/srep08890.
Deiko, R., Shtrygol, S., Kolobov, A., Simbirtsev, A., Mishchenko, M. (2017). The Antidepressant Activity Of The New Tetrapeptide Neuroprotector Kk-1, Homologous Of Acth15-18 Sequence (An Experimental Study). Journal Of Depression And Therapy, 1 (3), 10–17. doi: https://doi.org/10.14302/issn.2476-1710.jdt-16-1346.
Can, A., Dao, D. T., Terrillion, C. E., Piantadosi, S. C., Bhat, S., Gould, T. D. (2011). The Tail Suspension Test. Journal of Visualized Experiments, 58. doi: 10.3791/3769.
Vogel, H. (2008). Drug Discovery and Evaluation: Pharmacological Assays. 3rd ed. Berlin Heidelberg New York: Springer-Verlag, 2071.
Mironov, А. (Ed.). (2012). Guidelines for pre-clinical drug research. Part 1. 1st ed. Moscow: Grif and K., 944.
MOZ Ukrainy. (2014). Nakaz vid 25.12.2014 № 1003 «Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry depresii». zakon.rada.gov.ua. Available at: https://zakon.rada.gov.ua/rada/show/v1003282-14#Text.
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