Čes. slov. farm. 2021, 70(3):91-99 | DOI: 10.5817/CSF2021-3-91
Investigation of the effect of a modified fragment of neuropeptide Y on memory phases and extrapolation escape of animals
- Department of Pharmacology and Pharmacotherapy, National University of Pharmacy of the Ministry of Health of Ukraine, Kharkiv, Ukraine
The article presents a study of the effect of a modified fragment of neuropeptide Y (H-L-Ile-L-Asn-L-Leu-L-Nle-L-Ser-L-Arg-L-Asn-L-Arg-L-Tyr-NH2) named nonapeptide NP9 on the memory phases and extrapolation escape of animals. The study was performed in the passive avoidance test with intact animals, scopolamine-treated animals, and the extrapolation escape task. NP9 was investigated in the dose range of 0.04-0.4 mg/kg with a single intranasal administration. The comparison drug used peptide nootropic medicine Semax® (Met-Glu-His-Phe-Pro-Gly-Pro) at a dose of 0.1 mg/kg.
Efficiency was assessed by the retention latency, the percentage of animals that have reached the learning criterion, the number of incomplete attempts to enter, the antiamnestic activity index calculated by Butler's formula, and the number of animals that successfully performed the extrapolation escape task. Peptide NP9 was superior to Semax® in most indicators. It demonstrated the ability to improve memorization due to its effect on I phase of memory and facilitated extinction of negative experiences when administered after a stress stimulus. NP9 also increased the cognitive ability of animals in the conditions an aversive environment in the extrapolation escape test. Thus, peptide NP9 is promising for a further study as a potential drug for the treatment of cognitive impairment and therapy of post-traumatic stress disorder.
Keywords: modified fragment of neuropeptide Y; passive avoidance test; memory phases; extrapolation escape task
Received: January 28, 2021; Accepted: May 13, 2021; Published: March 1, 2021 Show citation
References
- Kienast C., Gunga H., Steinach M. Neuropeptide Y - Its role in human performance and extreme environments. REACH 2019; 14-15, 100032.
Go to original source...
- Benarroch E. Neuropeptide Y: Its multiple effects in the CNS and potential clinical significance. Neurology 2009; 72(11), 1016-1020.
Go to original source...
Go to PubMed...
- Havrylov I., Zagayko A. Prospects of pharmacological application of neuropeptide Y and its fragments. Medical and Clinical Chemistry 2019; 1, 113-119.
Go to original source...
- Brothers S., Wahlestedt C. Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO Mol. Med. 2010; 2(11), 429-439.
Go to original source...
Go to PubMed...
- Kornhuber J., Zoicas I. Neuropeptide Y prolongs nonsocial memory and differentially affects acquisition, consolidation, and retrieval of non-social and social memory in male mice. Sci. Rep. 2017; 7(1): 6821.
Go to original source...
Go to PubMed...
- Gøtzsche C., Woldbye D. The role of NPY in learning and memory. Neuropeptides 2016; 55, 79-89.
Go to original source...
Go to PubMed...
- Flood J., Baker M., Hernandez E., Morley J. Modulation of memory processing by neuropeptide Y varies with brain injection site. Brain Res. 1989; 503(1), 73-82.
Go to original source...
Go to PubMed...
- Flood J., Hernandez E., Morley J. Modulation of memory processing by neuropeptide Y. Brain Res. 1987; 421(1-2), 280-290.
Go to original source...
Go to PubMed...
- Bouchard P., Maurice T., St-Pierre S., Privat A., Quirion R. Neuropeptide Y and the calcitonin gene-related peptide attenuate learning impairments induced by MK-801 via a sigma receptor-related mechanism. Eur. J. Neurosci. 1997; 9(10), 2142-2151.
Go to original source...
Go to PubMed...
- Rangani R., Upadhya M., Nakhate K., Kokare D., Subhedar N. Nicotine evoked improvement in learning and memory is mediated through NPY Y1 receptors in rat model of Alzheimer's disease. Peptides 2012; 33(2), 17-328.
Go to original source...
Go to PubMed...
- Pedragosa-Badia X., Stichel J., Beck-Sickinger A. Neuropeptide Y receptors: how to get subtype selectivity. Front Endocrinol. 2013; 4, 5.
Go to original source...
Go to PubMed...
- Di L. Strategic approaches to optimizing peptide ADME properties. AAPS J 2015; 17(1), 134-143.
Go to original source...
Go to PubMed...
- Zagayko A., Havrylov I., Lytkin D. The study of the effect of the low molecular analog of neuropeptide Y on behavioral reactions in rats. Clin. Pharm. 2019; 23(4), 30-36.
Go to original source...
- Meredith M., Salameh T., Banks W. Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases. AAPS J 2015; 17(4), 780-787.
Go to original source...
Go to PubMed...
- Nair A., Jacob S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 2016; 7(2), 27.
Go to original source...
Go to PubMed...
- Kamenskiy A., Myasoedov N., Levitskaya N., Andreeva L., Sebentsova E., Glazova N., Manchenko D. Issledovanie spektra fiziologicheskoy aktivnosti analoga aktg 4-10 geptapeptida semaks. Neyrohimiya 2008; 25(1-2), 111-118.
- Eremin K., Kudrin V., Saransaari P., Oja S., Grivennikov I., Myasoedov N., Rayevsky K. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem. Res. 2005; 30(12), 493-500.
Go to original source...
Go to PubMed...
- Koroleva S., Myasoedov N. Semax as a universal drug for therapy and research. Biol. Bull. Russ. Acad. Sci. 2018; 45, 589-600.
Go to original source...
- Mironov А. Guidelines for preclinical drug research. Part 1. 1ed. Moscow: Grif and K 2012.
- Radionova K., Belnik A., Ostrovskaya R. The original nootropic drug "Noopept" eliminates memory deficit caused by blockade of M- and N-cholinergic receptors in rats. Bulletin of Experimental Biology and Medicine 2008; 146(1), 65-68.
Go to original source...
Go to PubMed...
- Bondarenko N. The selective effect of neuroleptics on a dopamine-dependent behavioral disorder in rats in the extrapolation escape test. Bulletin of Experimental Biology and Medicine 1990; 110(11), 506-508.
Go to original source...
- Voronkov A., Nigaryan S., Pozdnyakov D. Cerebroprotective effect of some phenolic acids under conditions of experimental brain ischemia. Pharmacy & Pharmacology 2019; 7(6), 32-338.
Go to original source...
- Day H., Stevenson C. The neurobiological basis of sex differences in learned fear and its inhibition. Eur. J. Neurosci. 2020; 52(1), 2466-2486.
Go to original source...
Go to PubMed...
- Hock F. Drug Discovery and Evaluation: Pharmacological Assays. Berlin. Heidelberg: Springer Berlin Heidelberg 2020.
- Volodina M., Sebentsova E., Glazova N., Levitskaya N., Andreeva L., Manchenko D., Kamensky A., Myasoedov N. Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats. Bull. Exp. Biol. Med. 2012; 152(5), 560.
Go to original source...
Go to PubMed...
- Bakhmet A., Koplik E. Antistress effect of Semax in the course of recovery of spleen lymphoid structures after the stress in rats with different behavioral activity. Bull. Exp. Biol. Med. 2012; 153(5), 1-3.
Go to original source...
Go to PubMed...
- Levitskaia N., Vilenskii D., Sebentsova E., Anreeva L., Kamenskii A., Miasoedov N. Influence of Semax on the emotional state of white rats in the norm and against the background of cholecystokinin-tetrapeptide action. Biology Bulletin 2010; 2(23), 1-7.
Go to original source...
- Yatsenko K., Glazova N., Inozemtseva L., Andreeva L., Kamensky A., Grivennikov I., Levitskaya N., Dolotov O., Myasoedov N. Heptapeptide semax attenuates the effects of chronic unpredictable stress in rats. Dokl. Biol. Sci. 2013; 453, 353.
Go to original source...
Go to PubMed...
- Seredin S., Melkumian D., Val'dman E., Iarkova M., Seredina T., Voronin M., Lapitskaia A. Effects of afobazole on the BDNF content in brain structures of inbred mice with different phenotypes of emotional stress reaction. Eksp. Klin. Farmakol. 2006; 69(3), 3-6.
- Paton C. Benzodiazepines and disinhibition: A review. Psychiatric Bulletin 2002; 26(12), 460-462.
Go to original source...
- Mancuso C. E., Tanzi M. G., Gabay M. Paradoxical reactions to benzodiazepines: literature review and tre atment options. Pharmacotherapy 2004; 24(9), 1177- 1185.
Go to original source...
Go to PubMed...
- Saïas T., Gallarda T. Réactions d'agressivité sous benzodiazépines: une revue de la littérature. L'Encéphale, 2008; 34(4), 330-336.
Go to original source...
Go to PubMed...
- Tasan R., Verma D., Wood J., Lach G., Hörmer B., de Lima T. The role of Neuropeptide Y in fear conditioning and extinction. Neuropeptides 2016; 55, 111-126.
Go to original source...
Go to PubMed...
- Lach G., de Lima T. Role of NPY Y1 receptor on acquisition, consolidation and extinction on contextual fear conditioning: Dissociation between anxiety, locomotion and non-emotional memory behavior. Neurobiol. Learn Mem. 2013; 103, 26-33.
Go to original source...
Go to PubMed...
- Verma D., Tasan R., Herzog H., Sperk G. NPY controls fear conditioning and fear extinction by combined action on Y 1 and Y 2 receptors. Br. J. Pharmacol. 2012; 166(4), 1461-1473.
Go to original source...
Go to PubMed...