Skip to main content
SpringerLink
Log in

Studies of the Role of Brain Melanocortin Receptors in Suppressing Food Consumption in Ether Stress in Mice

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

The melanocortin (MC) system controls food consumption in the resting state. Stress suppresses food consumption. It is not clear whether the brain MC system is involved in the development of stress anorexia in mice. The aim of the present work was to study the influences of pharmacological blockade and activation of brain MC receptors on food consumption on the background of stress. Mice (male C57Bl/6J) were subjected to ether stress (ether anesthesia for 0.5 min) before administration of physiological saline or a synthetic nonselective antagonist (SHU9119) or agonist (melanotan II) of MC receptors into the lateral ventricle. Food consumption in all mice was stimulated by prior 17-h starvation. Ether stress decreased food consumption and increased the blood corticosterone level and the hypothalamic AgRP gene mRNA (a natural antagonist of MC receptors) level 1 h after application. Pharmacological blockade of central MC receptors on the background of stress weakened stress anorexia and decreased the hypothalamic AgRP mRNA level, while activation exacerbated stress anorexia and hypercorticism. Thus, these studies showed that the central MC system is involved in the development of stress anorexia in mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. N. M. Bazhan, E. N. Makarova, A. Yu. Shevchenko, and T. V. Yakovleva, “Repeated emotional stress prevents the development of melanocortin obesity and type 2 diabetes in mice with the Agouti yellow mutation,” Ros. Fiziol. Zh., 93, No. 11, 1237–1244 (2007).

    CAS  Google Scholar 

  2. A. A. Tinnikov and N. M. Bazhan, “Assay of glucocorticoids in plasma and adrenal incubation medium by competitive hormone binding by proteins without preliminary extraction,” Lab. Delo, No. 12, 709–713 (1984).

  3. Z. A. Abdel-Malik, “Melanocortin receptors: their functions and regulation by physiological agonists and antagonists,” Cell Mol. Life Sci., 58, No. 3, 434–441 (2001).

    Article  Google Scholar 

  4. N. M. Bazhan, T. V. Yakovleva, A. Y. Kazantseva, and E. N. Makarova, “Exaggerated anorexigenic response to restraint stress in Ay mice is associated with elevated CRFR2 mRNA expression in the hypothalamus,” Physiol. Behav., 120, No. 1, 19–25 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. N. Bazhan and D. Zelena, “Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis,” Brain Res. Bull., 95, No. 1, 46–53 (2013).

    Article  CAS  PubMed  Google Scholar 

  6. S. Chaki, S. Ogawa, Y. Toda, et al., “Involvement of the melanocortin MC3 receptor in stress-related behavior in rodents,” Eur. J. Pharmacol., 474, No. 1, 95–101 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. F. Chigr, F. Rachidi, C. Tardivel, et al., “Modulation of orexigenic and anorexigenic peptides gene expression in the rat DVC and hypothalamus by acute immobilization stress,” Front. Cell. Neurosci., doi: 10.3389/fncel.2014.000198. eCollection.

  8. M. J. Cullen, N. Ling, A. C. Foster, and M. A. Pelleymounter, “Urocortin, corticotropin releasing factor-2 receptors and energy balance,” Endocrinology, 142, No. 3, 992–999 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. W. A. Cupples, “Peptides that regulate food intake,” Am. J. Physiol. Regul. Integr. Comp. Physiol., 284, No. 6, 1370–1374 (2003).

    Article  Google Scholar 

  10. J. De Souza, A. A. Butler, and R. D. Cone, “Disproportionate inhibition of feeding in A(y) mice by certain stressors: a cautionary note,” Neuroendocrinology, 72, No. 1, 126–132 (2000).

    Article  PubMed  Google Scholar 

  11. W. S. Dhillo, C. J. Small, L. J. Seal, et al., “The hypothalamic melanocortin system stimulates the hypothalamo-pituitary-adrenal axis in vitro and in vivo in male rats,” Neuroendocrinology, 75, No. 4, 209–216 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. S. Fryer, G. Waller, and B. S. Kroese, “Stress, coping, and disturbed eating attitudes in teenage girls,” Int. J. Eat. Disord., 22, No. 4, 427–436 (1997).

    Article  CAS  PubMed  Google Scholar 

  13. K. Gartner, D. Buttner, K. Dohler, et al., “Stress response of rats to handling and experimental procedures,” Lab. Anim., 14, No. 3, 267–274 (1980).

    Article  CAS  PubMed  Google Scholar 

  14. H. J. Grill, A. B. Ginsberg, R. J. Seeley, and J. M. Kaplan, “Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding and body weight,” J. Neurosci., 18, No. 23, 10128–10135 (1998).

    CAS  PubMed  Google Scholar 

  15. R. B. Harris, J. Zhou, M. Shi, et al., “Overexpression of agouti protein and stress responsiveness in mice,” Physiol. Behav., 73, No. 4, 599–608 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. R. L. Hauger, V. Risbrough, O. Brauns, and F. M. Dautzenberg, “Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets,” CNS Neurol. Disord., Drug Targets, 5, No. 4, 453–479 (2006).

    Article  CAS  Google Scholar 

  17. J. J. G. Hillebrand, M. J. H. Kas, and R. A. H. Adan, “Alpha-MSH enhances activity-based anorexia,” Peptides, 26, No. 10, 1690–1696 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. T. Imaki, J. L. Nahan, C. Riber, et al., “Differential regulation of corticotropin-releasing factor mRNA in rat brain regions by glucocorticoids and stress,” J. Neurosci., 11, No. 3, 585–599 (1991).

    CAS  PubMed  Google Scholar 

  19. B. G. Irani, J. R. Holder, A. Todorovic, et al., “Progress in the development of melanocortin receptor selective ligands,” Curr. Pharm. Des., 10, No. 28, 3443–3479 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. M. J. Kas, A. W. Bruijnzeel, J. R. Haanstra, et al., “Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event,” J. Mol. Endocrinol., 35, No. 1, 159–164 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. J. Liu, J. C. Garza, H. V. Truong, et al., “The melanocortinergic pathway is rapidly recruited by emotional stress and contributes to stress-induced anorexia and anxiety-like behavior,” Endocrinology, 148, No. 11, 5531–5540 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. K. J. Lookingland, J. W. Gunnet, and K. E. Moore, “Stress-induced secretion of alpha-melanocyte-stimulating hormone is accompanied by a decrease in the activity of tuberohypophysial dopaminergic neurons,” Neuroendocrinology, 53, No. 1, 91–96 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. X. Y. Liu, G. S. Barsh, H. Akil, and S. J. Watson, “Interaction between α-melanocyte-stimulating hormone and corticotropin-releasing hormone in the regulation of feeding and hypothalamo-pituitary-adrenal responses,” J. Neurosci., 23, No. 21, 7863–7872 (2003).

    Google Scholar 

  24. S. Makino, K. Asaba, M. Nishiyama, and K. Hashimoto, “Decreased type 2 corticotropin-releasing hormone receptor mRNA expression in the ventromedial hypothalamus during repeated immobilization stress,” Neuroendocrinology, 70, No. 1, 160–167 (1999).

    Article  CAS  PubMed  Google Scholar 

  25. E. Minály, C. Fekete, R. M. Lechan, and Z. Liposits, “Corticotropinreleasing hormone-synthesizing neurons of the human hypothalamus receive neuropeptide Y-immunoreactive innervation from neurons residing primarily outside the infundibular nucleus,” Comp. Neurol., 446, No. 3, 235–243 (2002).

    Article  Google Scholar 

  26. K. D. Mul, B. M. Spruijt, J. H. Brakkee, and R. A. H. Adan, “Melanocortin MC4 receptor-mediated feeding and grooming in rodents,” Eur. J. Pharmacol., 719, No. 2, 192–201 (2013).

    Article  CAS  PubMed  Google Scholar 

  27. B. E. Murphy, “Some studies of the protein binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fl uids by competitive protein – binding radioassay,” J. Clin. Endocrinol. Metab., 27, 973–990 (1967).

    Article  CAS  PubMed  Google Scholar 

  28. S. Obici, Z. Feng, J. Tan, et al., “Central melanocortin receptors regulate insulin action,” J. Clin. Invest., 108, No. 7, 1079–1085 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. G. Paxinos and K. Franklin, The Mouse Brain in Stereotaxic Coordinates, Academic Press, San Diego (1997).

    Google Scholar 

  30. M. A. Pelleymounter, M. Joppa, N. Ling, and A. C. Foster, “Pharmacological evidence supporting a role for central corticotropin-releasing factor (2) receptors in behavioral, but not endocrine, response to environmental stress,” J. Pharmacol. Exp. Ther., 302, No. 1, 145–152 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. J. Preil, M. B. Müller, A. Gesing, et al., “Regulation of the hypothalamic-pituitary-adrenocortical system in mice defi cient for CRH receptors 1 and 2,” Endocrinology, 142, No. 11, 4946–4955 (2001).

    Article  CAS  Google Scholar 

  32. G. N. Smagin, L. A. Howell, D. H. Ryan, et al., “The role of CRF2 receptors in corticotropin-releasing factor- and urocortin-induced anorexia,” Neuroreport, 9, 1601–1606 (1998).

    Article  CAS  PubMed  Google Scholar 

  33. A. Tabarin, Y. Diz-Chaves, D. Consoli, et al., “Role of the corticotropin-releasing factor receptor type 2 in the control of food intake in mice: a meal pattern analysis,” Eur. J. Neurosci., 26, No. 8, 2303–2314 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. H. Van Herck, F. De Boer, A. P. M. Hesp, et al., “Orbital bleeding in rats while under diethylether anaesthesia does not influence telemetrically determined heart rate, body temperature, locomotor and eating activity when compared with anaesthesia alone,” Lab. Anim., 31, No. 1, 271–278 (1997).

    Article  PubMed  Google Scholar 

  35. A. V. Vergoni, A. Bertolini, J. E. Wikberg, and H. B. Schiöth, “Selective melanocortin MC4 receptor blockage reduces immobilization stress-induced anorexia in rats,” Eur. J. Pharmacol., 369, No. 1, 1–15 (1999).

    Article  Google Scholar 

  36. J. C. Von Frijtag, G. Croiset, W. H. Gispen, et al., “The role of central melanocortin receptors in the activation of the hypothalamus-pituitary-adrenal axis and the induction of excessive grooming,” Brit. J. Pharmacol., 123, No. 8, 1503–1508 (1998).

    Article  Google Scholar 

  37. B. Xu, E. H. Goulding, K. Zang, et al., “Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor,” Nat. Neurosci., 6, No. 7, 736–742 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Federal Research Center Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia

    N. M. Bazhan, E. V. Kulikova, E. N. Makarova, T. V. Yakovleva & A. Yu. Kazantseva

Authors
  1. N. M. Bazhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. V. Kulikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. N. Makarova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. V. Yakovleva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Yu. Kazantseva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. M. Bazhan.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 101, No. 12, pp. 1337–1346, December, 2012.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bazhan, N.M., Kulikova, E.V., Makarova, E.N. et al. Studies of the Role of Brain Melanocortin Receptors in Suppressing Food Consumption in Ether Stress in Mice. Neurosci Behav Physi 47, 438–443 (2017). https://doi.org/10.1007/s11055-017-0418-y

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-017-0418-y

Keywords

Search

Navigation