Impact of social stress in early ontogenesis on food addiction and ghrelin levels in the hypothalamus of rats

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Abstract

BACKGROUND: Factors that can trigger episodes of binge (compulsive) eating include psychological and physical stress. Our studies have shown that maternal deprivation in early ontogenesis leads to an increase in elements of gambling addiction in the Iowa Gambling Task test. This raises the question of the role of maternal deprivation in the development of other types of non-chemical addictions, particularly food addiction.

AIM: To study the role of ghrelin in the manifestation of food addiction elements in rats subjected to maternal deprivation in early ontogenesis.

MATERIALS AND METHODS: Wistar rats were separated from their mothers for 180 minutes daily from day 2 to day 12 after birth. Male rats aged 90–100 days were used in the experiments. To induce compulsive overeating, the animals were given a high-carbohydrate diet (a mixture based on chocolate paste) for 1 hour every third day for 1.5 months. Fifteen minutes before feeding, the chocolate paste was placed within 5 cm of the rat’s reach with visual contact. After compulsive overeating was established, the number and area of ghrelin-producing neuroendocrine cells in the hypothalamus were analyzed using immunohistochemistry in intact rats and animals subjected to maternal deprivation stress.

RESULTS: It was shown that intermittent consumption of the chocolate mixture predicted overeating in rats, independent of weight gain or obesity, as a result of compulsive overeating. In studying the effect of maternal deprivation on chocolate consumption, it was found that the average daily consumption in the maternal deprivation group increased (p < 0.001) compared to the control group. However, there was no significant difference in standard food consumption between the maternal deprivation and control groups. The number and area of ghrelin-producing neuroendocrine cells in the lateral portion of the medial arcuate nucleus of the hypothalamus were reduced in rats after maternal deprivation.

CONCLUSIONS: It was concluded that early psychogenic stress from maternal deprivation causes a dysregulation of the ghrelin system, contributing to elements of food addiction in rats.

About the authors

Andrey A. Lebedev

Institute of Experimental Medicine

Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425

Dr. Sci. (Biology), Professor

Russian Federation, Saint Petersburg

Andrey V. Droblenkov

Institute of Experimental Medicine

Email: droblenkov_a@mail.ru
ORCID iD: 0000-0001-5155-1484
SPIN-code: 8929-8601

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Sarng S. Pyurveev

Institute of Experimental Medicine; St. 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

Galina P. Kosyakova

Institute of Experimental Medicine; Saint Petersburg State Pediatric Medical University

Email: galkos1@mail.ru
ORCID iD: 0000-0001-7211-7839
SPIN-code: 9987-7041

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg; Saint Petersburg

Aleksandr A. Bezverkhiy

Institute of Experimental Medicine

Author for correspondence.
Email: bezveraa@mail.ru
Russian Federation, Saint Petersburg

Viktor 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 Petersburg

Maria A. Netesa

Institute of Experimental Medicine

Email: saintula@gmail.com
Russian Federation, Saint Petersburg

Petr 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 Petersburg

References

  1. Fenoglio KA, Brunson KL, Baram TZ. Hippocampal neuroplasticity induced by early-life stress: functional and molecular aspects. Front Neuroendocrinol. 2006;27(2):180–192. doi: 10.1016/j.yfrne.2006.02.001
  2. 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. doi: 10.1186/1471-244X-8-33
  3. Lang AJ, Aarons GA, Gearity J, et al. Direct and indirect links between childhood maltreatment, posttraumatic stress disorder, and women’s health. Behav Med. 2008;33(4):125–135. doi: 10.3200/BMED.33.4.125-136
  4. Tata D. Maternal separation as a model of early stress: Effects on aspects of emotional behavior and neuroendocrine function. Hellenic J Psychol. 2012;9:84–10.
  5. Naqavi MR, Mohammadi M, Salari V, et al. The relationship between childhood maltreatment and opiate dependency in adolescence and middle age. Addict Health. 2001;3(3–4):92–98.
  6. Nishi M, Horii-Hayashi N, Sasagawa T, Matsunaga W. Effects of early life stress on brain activity: implications from maternal separation model in rodents. Gen Comp Endocrinol. 2013;181:306–309. doi: 10.1016/j.ygcen.2012.09.024
  7. 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.2006.08.003
  8. Krupina NA, Shirenova SD, Khlebnikova NN. Prolonged social isolation, started early in life, impairs cognitive abilities in rats depending on sex. Brain Sci. 2020;10(11):799. doi: 10.3390/brainsci10110799
  9. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–660. doi: 10.1038/45230
  10. Chen C-Y, Asakawa A, Fujimiya M, et al. Ghrelin gene products and the regulation of food intake and gut motility. Pharmacol Rev. 2009;61(4):430–481. doi: 10.1124/pr.109.001958
  11. Gnanapavan S, Kola B, Bustin SA, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab. 2002;87(6):2988–2991. doi: 10.1210/jcem.87.6.8739
  12. Perello M, Sakata I, Birnbaum S. Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol Psychiatry. 2010;67(9):880–886. doi: 10.1016/j.biopsych.2009.10.030
  13. Carroll ME, France CP, Meisch RA, et al. Food deprivation increases oral and intravenous drug intake in rats. Science (New York). 1979;205(4403):319–321. doi: 10.1126/science.36665
  14. Kharbanda KK, Farokhnia M, Deschaine SL, et al. Role of the ghrelin system in alcohol use disorder and alcohol-associated liver disease. A narrative review. Alcohol Clin Exp Res. 2022;46(12): 2149–2159. doi: 10.1111/acer.14967
  15. Jerlhag E, Egecioglu E, Dickson SL, Engel JA. Glutamatergic regulation of ghrelin-induced activation of the mesolimbic dopamine system. Addict Biol. 2011;16(1):82–91. doi: 10.1111/j.1369-1600.2010.00231.x
  16. Patterson ZR, Ducharme R, Anisman H, Abizaid A. Altered metabolic and neurochemical responses to chronic unpredictable stressors in ghrelin receptor-deficient mice. Eur J Neurosci. 2010;32(4):632–639. doi: 10.1111/j.1460-9568.2010.07310
  17. Shabanov PD, Yakushina ND, Lebedev AA. Pharmaco¬logy of peptide mechanisms of gambling behavior in rats. Journal of addiction problems. 2020;(4):24–44. EDN: JBUQJN doi: 10.47877/0234-0623_2020_4_24
  18. Lebedev AA, Karpova IV, Bychkov ER, et al. The ghrelin antagonist [D-LYS3]-GHRP-6 decreases signs of risk behavior in a model of gambling addiction in rats by altering dopamine and serotonin metabolism. Neurosci Behav Physiol. 2022;52(3):415–421. doi: 10.1007/s11055-022-01255-x
  19. 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
  20. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th edit. Arlington: American Psychiatric Publishing; 2013. doi: 10.1176/appi.books.9780890425596
  21. Lebedev AА, Pyurveev SS, Nadbitova ND, et al. Reduction of compulsive overeating in rats caused by maternal deprivation in early ontogenesis with the use of a new ghrelin receptor antagonist agrelax. Reviews on Clinical Pharmacology and Drug Therapy. 2023;21(3):255–262. EDN: SLBOTQ doi: 10.17816/RCF562841
  22. Lisovsky AD, Popkovsky NA, Bobkov PS, Droblenkov AV. Morphology of kisspeptin-producing nuclei in the rat hypothalamus. Medical Academic Journal. 2022;22(4):69–76. EDN: OQPBSD doi: 10.17816/MAJ109714
  23. Nathan PJ, Bullmore ET. From taste hedonics to motivational drive: central µ-opioid receptors and binge-eating behavior. Int J Neuropsychopharmacol. 2009;12(7):995–1008. doi: 10.1017/S146114570900039X
  24. Cabral A, Suescun O, Zigman JM, Perello M. Ghrelin indirectly activates hypophysiotropic CRF neurons in rodents. PloS One. 2012;7(2):e31462. doi: 10.1371/journal.pone.0031462
  25. Lebedev AA, Moskalev AR, Abrosimov ME, et al. Effect of neuropeptide Y antagonist BMS193885 on overeating and emotional responses induced by social isolation in rats. Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(2):189–202. EDN: OWSTEO doi: 10.17816/RCF192189-202
  26. Alvarez-Crespo M, Skibicka KP, Farkas I, et al. The amygdala as a neurobiological target for ghrelin in rats: Neuroanatomical, electrophysiological and behavioral evidence. PloS One. 2012;7(10):e46321. doi: 10.1371/ journal. pone.0046321
  27. 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
  28. Sawchenko PE, Swanson LW. Localization, colocalization, and plasticity of corticotropin-releasing factor immunoreactivity in rat brain. Fed Proc. 1985;44(1):221–227.
  29. Pina MM, Cunningham CL. Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit. Neurobiol Learn Mem. 2017;137:83–91. doi: 10.1016/j.nlm.2016.11.013
  30. Karpova IV, Bychkov ER, Lebedev AA, Shabanov PD. Monoaminergic effects of the unilateral blockade of orexin receptors (OX1R) in the enlarged amygdala under psychostimulant action. Psychopharmacology and biological narcology. 2023;14(1):49–62. EDN: VIUURH doi: 10.17816/phbn321621
  31. Willesen MG, Kristensen P, Rømer J. Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat. Neuroendocrinology. 1999;70(5):306–316. doi: 10.1159/000054491
  32. Schmidt MV, Levine S, Alam S, at al. Metabolic signals modulate hypothalamic-pituitary-adrenal axis activation during maternal separation of the neonatal mouse. J Neuroendocrinol. 2006;18(11): 865–874. doi: 10.1111/j.1365-2826.2006.01482.x
  33. Shabanov PD, Lebedev AA, Mescherov ShK. Dopamine and reinforcing systems of the brain. Saint Petersburg: Lan; 2002. 208 p. (In Russ.)
  34. 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 EDN: QHQMQH doi: 10.17816/RCF15438-45
  35. 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 and biological narcology. 2023;14(1):69–79. EDN: LPJPUM doi: 10.17816/phbn321624
  36. Raptanova VA, Droblenkov AV, Lebedev AA, et al. Reactive changes of gastric mucosa and reduction of desacyl grelin in rat brain due to psychoemotional stress. Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(2):203–210. EDN: QJFGXA doi: 10.17816/RCF192203-210
  37. Blazhenko AA, Khokhlov PP, Lebedev AA, et al. Ghrelin levels in different brain regions in Danio rerio exposured to stress. Psychopharmacology and biological narcology. 2022;13(3):37–42. EDN: BFOJYK doi: 10.17816/phbn267375

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