Effect of antorex, a new antagonist of orexin receptors, on binge eating in rats caused by weaning from the mother in early ontogenesis
- Authors: Lebedev A.A.1, Pyurveev S.S.1,2, Nadbitova N.D.1, Bychkov E.R.1, Lizunov A.V.1, Lukashkova V.V.1, Evdokimova N.R.1, Lebedev V.A.1, Shabanov P.D.1
-
Affiliations:
- Institute of Experimental Medicine
- Saint Petersburg State Pediatric Medical University
- Issue: Vol 22, No 1 (2024)
- Pages: 67-73
- Section: Original study articles
- URL: https://journals.rcsi.science/RCF/article/view/258601
- DOI: https://doi.org/10.17816/RCF622939
- ID: 258601
Cite item
Abstract
BACKGROUND: Research on the elements of food addiction in animal models shows that its manifestations are attributed to intermittent consumption of high-calorie foods. Chronic stress in ontogenesis can cause episodes of binge eating or dietary restrictions such as anorexia.
AIM: This study aimed to investigate the effect of a new orexin receptor antagonist antorex on binge eating in a rat model of maternal neglect.
MATERIALS AND METHODS: Mature male rats weaned from their mothers for 3 h after birth from days 2 to 12 received a high-carbohydrate diet every third day for 1 h for 45 days. Moreover, high-calorie food was placed within 5 cm of visual contact 15 min before feeding. Antorex, an orexin receptor antagonist, was administered intranasally at a dose of 1 µg/1µL for a total of 20 µL for 7 days.
RESULTS: Intermittent consumption of high-calorie food products induced binge eating in rats. The frequency of the signs of binge eating increased after chronic weaning stress. The consumption of standard briquette feed was not altered. Intranasal administration of both the orexin receptor antagonist antorex reduced the manifestations of food addiction in rats after maternal deprivation under conditions of intermittent consumption of high-calorie food compared with controls. Standard food intake did not differ relative to the control group both before and after аntorex administration.
CONCLUSIONS: The results suggest new ways to study and synthesize peptide drugs based on orexin and its antagonists for the correction of food addiction caused by chronic stress in ontogenesis.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Andrey A. Lebedev
Institute of Experimental Medicine
Author for correspondence.
Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425
SPIN-code: 4998-5204
Dr. Sci. (Biology), Professor
Russian Federation, Saint PetersburgSarng S. Pyurveev
Institute of Experimental Medicine; Saint Petersburg State Pediatric Medical University
Email: dr.purveev@gmail.com
ORCID iD: 0000-0002-4467-2269
SPIN-code: 5915-9767
Russian Federation, Saint Petersburg; Saint Petersburg
Natalia D. Nadbitova
Institute of Experimental Medicine
Email: natali_805@mail.ru
MD, Cand. Sci. (Medicine)
Russian Federation, Saint PetersburgEvgeny R. Bychkov
Institute of Experimental Medicine
Email: bychkov@mail.ru
ORCID iD: 0000-0002-8911-6805
SPIN-code: 9408-0799
MD, Cand. Sci. (Medicine)
Russian Federation, Saint PetersburgAleksey V. Lizunov
Institute of Experimental Medicine
Email: izya12005@yandex.ru
Cand. Sci. (Biology)
Russian Federation, Saint PetersburgValeria V. Lukashkova
Institute of Experimental Medicine
Email: valeriyalu15@gmail.com
Russian Federation, Saint Petersburg
Natalia R. Evdokimova
Institute of Experimental Medicine
Email: natali_805@mail.ru
Cand. Sci. (Biology)
Russian Federation, Saint PetersburgViktor A. Lebedev
Institute of Experimental Medicine
Email: vitya-lebedev-57@mail.ru
ORCID iD: 0000-0002-1525-8106
SPIN-code: 1878-8392
Cand. Sci. (Biology)
Russian Federation, Saint PetersburgPetr D. Shabanov
Institute of Experimental Medicine
Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477
Dr. Sci. (Medicine), Professor
Russian Federation, Saint PetersburgReferences
- Boggiano MM, Artiga AI, Pritchett CE, et al. High intake of palatable food predicts binge-eating independent of susceptibility to obesity: An animal model of lean vs obese binge-eating and obesity with and without binge-eating. Int J Obes. 2007;31(9):1357–1367. doi: 10.1038/sj.ijo.0803614
- Nathan P, Bullmore E. From taste hedonics to motivational drive: central μ-opioid receptors and binge-eating behaviour. Int J Neuropsychopharmacol. 2009;12(07):995–1008. doi: 10.1017/s146114570900039x
- Aston-Jones G, Smith RJ, Sartor H, et al. Lateral hypothalamic orexin/hypocretin neurons: A role in reward-seeking and addiction. Brain Res. 2010;1314:74–90. doi: 10.1016/j.brainres.2009.09.106
- De Lecea L. Hypocretins and the neurobiology of sleep-wake mechanisms. Prog Brain Res. 2012;198:234–248. doi: 10.1016/B978-0-444-59489-1.00003-3
- Lebedev AA, Bessolova YN, Efimov NS, et al. Role of orexin peptide system in emotional overeating induced by brain reward stimulation in fed rats. Res Results Pharmacol. 2020;6(1):81–91. doi: 10.3897/ rrpharmacology.6.52180
- Arendt DH, Hassell J, Li H, et al. Anxiolytic function of the orexin 2/hypocretin A receptor in the basolateral amygdala. Psychoneuroendocrinology. 2014;40:17–26. doi: 10.1016/j.psyneuen.2013.10.010
- Catani C, Jacob N, Schauer E, et al. Family violence, war, and natural disasters: A study of the effect of extreme stress on children’s mental health in Sri Lanka. BMC Psychiatry. 2008;8(33):1–10. doi: 10.1186/1471-244X-8-33
- Tata D. Maternal separation as a model of early stress: Effects on aspects of emotional behavior and neuroendocrine function. Hellenic Journal of Psychology. 2012;9:84–101.
- Naqavi MR, Mohammadi M, Salari V, et al. The relationship between childhood maltreatment and opiate dependency in adolescence and middle age. Addict Health. 2011;3(3–4):92–98.
- Moffett MC, Vicentic A, Kozel M, et al. Maternal separation alters drug intake patterns in adulthood in rats. Biochem Pharmacol. 2007;73(3):321–330. doi: 10.1016/j.bcp.2006.08.00315
- Lebedev AA, Lukashkova VV, Pshenichnaya AG, et al. A new ghrelin receptor antagonist agrelax participates in the control of emotional-explorative behavior and anxiety in rats // Psychopharmacology & biological narcology. 2023;14(1):69–79. doi: 10.17816/phbn321624
- Piccoli L, Micioni Di Bonaventura MV, Cifani C, et al. Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats Neuropsychopharmacology. 2012;37(9):1999–2011. doi: 10.1038/npp.2012.48
- Rossi MA, Stuber GD. Overlapping brain circuits for homeostatic and hedonic feeding. Cell Metab. 2018;27(1):42–56. doi: 10.1016/j.cmet.2017.09.021
- Roik RO, Lebedev AA, Shabanov PD. The value of extended amygdala structures in emotive effects of narcogenic with diverse chemical structure. Research Results in Pharmacology. 2019;5(3):11–19. doi: 10.3897/npharmacology.5.38389
