Email this article 
Post a Comment 
Effect of neuropeptide Y antagonist BMS193885 on overeating and emotional responses induced by social isolation in rats
- Authors: Lebedev A.A.1, Moskalev A.R.1, Abrosimov M.E.1, Vetlugin E.A.1, Pshenichnaya A.G.1, Lebedev V.A.1, Evdokimova N.R.1, Bychkov E.R.1, Shabanov P.D.1
-
Affiliations:
- Institute of Experimental Medicine
- Issue: Vol 19, No 2 (2021)
- Pages: 189-202
- Section: Original articles
- URL: https://journals.eco-vector.com/RCF/article/view/77310
- DOI: https://doi.org/10.17816/RCF192189-202
Cite item
Open Access
Access granted
Abstract
BACKGROUND: Chronic stress of social isolation is associated with an increased risk of mental illness, such as atypical depression, and is usually accompanied by hyperphagia and weight gain. We have previously shown that the NPY antagonist Y1R BMS193885 reduces the conditioned place preference of ethanol. The involvement of NPY receptors in non-chemical forms of addiction is assumed.
AIM: Was to analyze the effects of NPY Y1R BMS193885 on emotional responses and elements of bindge eating in rats caused by rearing in social isolation.
MATERIALS AND METHODS: We used the tests “open field”, “elevated plus maze”, Porsolt’s forced swimming test, “resident intruder” test and method of conditioned eating test in well-fed rats.
RESULTS: The level of depression, negative emotionality and locomotor activity increased in rats reared in isolation. After intranasal administration of BMS193885 high locomotor activity was maintained, but investigating activity increased in isolated rats. Isolated animals showed an increase in body weight at the 6th week of life. By to the 9th week, the body weight of the isolated rats was significantly higher than in animals reared in the community (р ≤ 0.05). Intranasal administration of 20 μg BMS193885 for 1 week caused a decrease in feed intake in both groups of animals (р ≤ 0.05). Isolated rats began to consume the same amount of food as animals reared in the community after administration of 0.9% NaCl solution. At the same time, elements of bindge eating were observed in the study of the conditioned food test in satiated isolated rats, which did not appear after 1 week of intranasal administration of 20 μg of BMS193885.
CONCLUSIONS: The data obtained prove that rats reared in isolation can be considered as a potential model for binge eating, the basis for metabolic imbalance caused by individual housing in rodents. These considerations are of particular relevance when evaluating the effectiveness of drugs, diet, or other interventions for metabolic health and depressive disorders.
Full Text
About the authors
Andrei A. Lebedev
Institute of Experimental Medicine
Author for correspondence.
Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425
SPIN-code: 4998-5204
PhD, Dr. Sci. (Biol.), Professor
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgAleksandr R. Moskalev
Institute of Experimental Medicine
Email: dr.moskalev91@gmail.com
postgraduate student
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgMaksim E. Abrosimov
Institute of Experimental Medicine
Email: abrosimovmaxim1990@mail.ru
postgraduate student
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgEduard A. Vetlugin
Institute of Experimental Medicine
Email: vetedd@gmail.com
postgraduate studen
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgAnna G. Pshenichnaya
Institute of Experimental Medicine
Email: pscanna@mail.ru
ingeneer
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgVikto A. Lebedev
Institute of Experimental Medicine
Email: aalebedev-iem@rambler.ru
PhD, Cand. Sci. (Biol.)
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgNatalia R. Evdokimova
Institute of Experimental Medicine
Email: enatalyar@mail.ru
SPIN-code: 2087-0058
PhD, Cand. Sci. (Biol.)
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgEugeny R. Bychkov
Institute of Experimental Medicine
Email: bychkov@mail.ru
ORCID iD: 0000-0002-8911-6805
SPIN-code: 9408-0799
PhD, Cand. Sci. (Biol.)
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgPetr D. Shabanov
Institute of Experimental Medicine
Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477
MD, PhD, Dr. Sci. (Med.), Professor
Russian Federation, 12, Acad. Pavlov str., 197376, Saint PetersburgReferences
- Karpova IV, Mikheyev VV, Bychkov YR, et al. Asymmetry in the content of brain monoamines of balb/c mice reared in social isolation conditions. Reviews on clinical pharmacology and drug therapy. 2012;10(4):42–48. (In Russ.) doi: 10.17816/RCF10442-48
- Karpova IV, Mikheyev VV, Bychkov YR, et al. Social isolation changes asymmetrically the content of monoamines in the balb/c mice brain. Vestnik of the Smolensk state medical academy. 2012;11(3):3–9. (In Russ.)
- Koroleva SV, Ashmarin IP. Neiropeptid Y: mnogoobrazie i kazhushchayasya protivorechivost’ funktsii. Analiz vozmozhnykh oposredovannykh ehffektov. Progress in physiological science. 2000;31:31–46. (In Russ.)
- Lebedev AA, Pshenichnaya AG, Yakushina ND, et al. Effect of astressin, a corticoliberin antagonist, on aggression and anxiety-fobic states in male rats reared in social isolation. Reviews on clinical pharmacology and drug therapy. 2017;15(3):38–47. (In Russ.) doi: 10.17816/RCF15338-47
- Lebedev AA, Shabanov PD, Chepurnova NE. Lateralizovannye ehffekty analoga melanostatina alaptida u krys, vyrashchennykh v izolyatsii i soobshchestve. Neuroscience and Behavioral Physiology. 1994;80(10):24–31. (In Russ.)
- Lebedev AA, Petrov ES. Povedencheskie reaktsii pri razdrazhenii ehmotsiogennykh zon mozga u krys s razlichnym individual’nym opytom. Neuroscience and Behavioral Physiology. 1986;36(3): 496–502. (In Russ.)
- Lebedev AA, Petrov ES, Vartanyan GA. Rol’ individual’nogo opyta v rannem ontogeneze v formirovanii podkreplyayushchikh sistem mozga krys. Neuroscience and Behavioral Physiology. 1983;33(2):363–365. (In Russ.)
- Lebedev AA, Loseva IV, Shabanov PD. Ehffekty dofaminergicheskikh sredstv na samostimulyatsiyu lateral’nogo gipotalamusa i obmen dofamina v mozge krys-izolyantov s razrusheniem ventral’noi oblasti pokryshki. Neuroscience and Behavioral Physiology. 1995;45(2):305–401. (In Russ.)
- Lebedev AA, Bychkov ER, Nikolaev SV, et al. Vliyanie fenamina na soderzhanie dofamina, noradrenalina, serotonina i ikh metabolitov v dofaminergicheskikh strukturakh mozga krys s razlichnym individual’nym opytom. Narcology. 2002;1(12):2–6. (In Russ.)
- Lebedev AA, Russanovsky VV, Makarova TM, Shabanov PD. Comparison of intraspecific and individual behavior of male and female rats reared in conditions of social isolation. Psychopharmacology and Biological Narcology. 2005;5(1):861–865. (In Russ.)
- Lebedev AA, Makarova TM, Rusanovskii VV, Shabanov PD. Organizatsiya razlichnykh form vnutrividovogo i individual’nogo povedeniya samtsov i samok krys s obychnym i ogranichennym zoosotsial’nym opytom. Clinical pathophysiology. 2004;(2):47–52. (In Russ.)
- Moskalyev AR, Abrosimov ME, Vetlugin EA, et al. Pharmacological analysis of the effects of the neuropeptide y antagonist BMS193885 on the emotional, intraspecies behavior and reinforcing properties of ethanol in rats. Reviews on clinical pharmacology and drug therapy. 2020;18(2):131–138. (In Russ.) doi: 10.17816/RCF182131-138
- Roik RO, Lebedev AA, Russanovsky VV, et al. Estimation of antidepressant effects with different mode of action on the model of depression-like state due to social isolation. Psychopharmacology and biological narcology. 2004;4(1):590–593. (In Russ.)
- Shabanov PD, Vinogradov PM, Lebedev AA, et al. Ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. Reviews on clinical pharmacology and drug therapy. 2017;15(4):38–45. (In Russ.) doi: 10.17816/RCF15438-45
- Shabanov PD, Vinogradov PM, Lebedev AA, Morozov VI. Ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. Psikhicheskoe zdorov’e. 2017;15(5):3–11. (In Russ.) doi: 10.17816/RCF15438-45
- Shabanov PD, Roik RO, Lebedev AA, Strel’tsov VF. Effects of antidepressants in models of brain self-stimulation and place preference after prolong social isolation and alcoholization. Russian Journal of Experimental and Clinical Pharmacology. 2006;69(4):60–65. (In Russ.)
- Shabanov PD, Lebedev AA, Rusanovskii VV. Povedencheskie i neirokhimicheskie posledstviya sotsial’noi izolyatsii. Reviews on clinical pharmacology and drug therapy. 2003;2(4):26–44. (In Russ.)
- Shabanov PD, Lebedev AA, Meshcherov ShK. Dofamin i podkreplyayushchie sistemy mozga. Saint Petersburg: Lan’, 2002. 208 p. (In Russ.)
- Shabanov PD, Lebedev AA, Nozdrachev AD. Funktsional’noe markirovanie sostoyaniya sotsial’noi izolirovannosti s pomoshch’yu analoga melanostatina alaptida u krys. Doklady Akademii nauk. 1998;358(2):283–285. (In Russ.)
- Shabanov PD, Meshcherov ShK, Lebedev AA. Sindrom sotsial’noi izolyatsii. Saint Petersburg: Ehlbi-SPb, 2004. (In Russ.)
- Shabanov PD, Rusanovskii VV, Lebedev AA. Zoosotsial’noe povedenie mlekopitayushchikh. Saint Petersburg: Ehlbi-SPb, 2006. 202 p. (In Russ.)
- Shabanov PD, Egereva EA, Lebedev AA. Modelling the autistic spectrum disorders by early social isolation in rats. Vestnik of the Smolensk state medical academy. 2018;17(2):5–15. (In Russ.)
- Antal-Zimanyi I, Bruce MA, Leboulluec KL, et al. Pharmacological characterization and appetite suppressive properties of BMS-193885, a novel and selective neuropeptide Y(1) receptor antagonist. Eur J Pharmacol. 2008;590(1–3):224–232. doi: 10.1016/j.ejphar.2008.06.032
- Blomqvist A, Lundell M, Larhammar D. Strong evolutionary conservation of neuropeptide Y between mammals, chicken, goldfish and horned shark. Ann NY Acid Sci. 1990;611(1):611–618. doi: 10.1111/j.1749-6632.1990.tb48956.x
- Corwin RL, Avena NM, Boggiano MM. Feeding and reward: perspectives from three rat models of binge eating. Physiol Behav. 2011;104(1):87–97. doi: 10.1016/j.physbeh.2011.04.041
- Dandekar MP, Singru PS, Kokare DM, SubhedarNK. Cocaine- and amphetamine-regulated transcript peptide (CART) plays a role in the manifestation of depression: social isolation and olfactory bulbectomy models reveal unifying principles. Neuropsychopharmacology. 2009;34:1288–1300. doi: 10.1038/npp.2008.201
- Fiala B, Snow FM, Greenouch WT. Impoverished rats weigh more than ‘enriched’ rats because they eat more. Dev Psychobiol. 1977;10(6):537–541. doi: 10.1002/dev.420100607
- Fulford AJ, Marsden CA. Conditioned release of 5-hydroxytryptamine in vivo in the nucleus accumbens following isolation-rearing in the rat. Neuroscience. 1998;83:481–487.
- Galef BG. Weaning from mothers milk to solid foods. The developmental psychobiology of self-selection of foods by rats. Ann NY Acad Sci. 1992;662(1):37–52. doi: 10.1111/j.1749-6632.1992.tb22853.x
- Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides. 2004;38(4):213–219. doi: 10.1016/j.npep.2004.05.002
- Kokare DM, Dandekar MP, Singru PS, et al. Involvement of alpha-MSH in the social isolation induced anxiety- and depression-like behaviors in rat. Neuropharmacology. 2010;58(7):1009–1018. doi: 10.1093/ijnp/pyx041
- Krupina NA, Khlebnikova NN, Narkevich VB, et al. The levels of monoamines and their metabolites in the brain structures of rats subjected to two- and three-month-long social isolation. Bulletin of Experimental Biology and Medicine. 2020;168(5):605–609. doi: 10.3389/fneur.2019.01380
- Lindner D, Stichel J, Beck-Sickinger AG. Molecular recognition of the NPY hormone family by their receptors. Nutrition. 2008;24(9):907–917. doi: 10.1016/j.nut.2008.06.025.
- Lebedev AA, Panchenko GN, Shabanov PD. Dopaminergic mode of action for melanostatine analogue in animal model of social isolation. Neuroendocrinology Letters. 1993;15(4):320.
- Lopak V, Eikelboom R. Modulation of the pair housing induced feeding suppression. Physiol Behav. 2004;83(1):157–164. doi: 10.1016/S0031-9384(04)00339-7
- Mahajan T, Crown A, Checkley S, et al. Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life. Eur J Endocrinol. 2004;151(3):325–332. doi: 10.1530/eje.0.1510325
- Mayer J. Overweight: causes, cost, and control. Prentice-Hall: Englewood Cliffs, New Jersey, 1968.
- Michel MC, Beck-Sickinger A, Cox H, et al. XVI International Union of Pharmacology recommendation for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev. 1998;50:143–150.
- Nonogaki K, Nozue K, Oka Y. Social isolation affects the development of obesity and type 2 diabetes in mice. Endocrinology. 2007;148(10):4658–4666. doi: 10.1523/JNEUROSCI.2584-06
- Panchenko GN, Lebedev AA, Shabanov PD. Comparison of the effects of dopamine agonists on self-stimulation of the hypothalamus with lesioning of mesolimbic brain structures in rats reared in conditions of social isolation. Neurosci Behav Physiol. 1998;28(2):130–135. doi: 10.1007/BF02461958
- Parker G, Roy K, Wilhelm K, et al. Atypical depression: a reappraisal. Am J Psychiatry. 2002;159(9):1470–1479. doi: 10.1176/appi.ajp.159.9.1470
- Pérez C, Canal JR, Domínguez E, et al. Individual housing influences certain biochemical parameters in the rat. Lab Anim. 1997;31(4):357–361. doi: 10.1258/002367797780596158
- Ryu V, Yoo SB, Kang DW, et al. Post-weaning isolation promotes food intake and body weight gain in rats that experienced neonatal maternal separation. Brain Res. 2009;1295:127–134. doi: 10.3389/fnins.2011.00012
- Sahakian BJ, Burdess C, Luckhurst H, Trayhurn P. Hyperactivity and obesity: the interaction of social isolation and cafeteria feeding. Physiol Behav. 1982;28(1):117–124. doi: 10.1016/0031-9384(82)90112-3
- Serra M, Pisu MG, Littera M, et al. Social isolation-induced decreases in both the abundance of neuroactive steroids and GABA(A) receptor function in rat brain. J Neurochem. 2000;75(2):732–740. doi: 10.1046/j.1471-4159.2000.0750732.x
- Tatemoto K, Carlquist M, Mutt V. Neuropeptide Y – a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptides. Nature. 1982;269:659–660.
- Thorsell A, Slawecki CJ, Khoury AE, et al. The effects of social isolation on neuropeptide Y levels, exploratory and anxiety-related behaviors in rats. Pharmacol Biochem Behav. 2006;83(1):28–34. doi: 10.1016/j.pbb.2005.12.005
- Thoa NB, Tizabi Y, Jacobowitz DM. The effect of isolation on catecholamine concentration and turnover in discrete areas of the rat brain. Brain Res. 1977;131(2):259–269. doi: 10.1016/0006-8993(77)90519-4
- Xapelli S, Agasse F, Ferreira R, et al. Neuropeptide Y as an endogenous antiepileptic, neuroprotective and pro-neurogenic peptide. Recent Patents on CNS. Drug Discovery. 2006;1(3):315–324. doi: 10.2174/157488906778773689
- Walker DM, Cunningham AM, Gregory JK, Nestler EJ. Long-term behavioral effects of post-weaning social isolation in males and females. Front Behav Neurosci. 2019;13:66. doi: 10.3389/fnbeh.2019.00066.
