EFFECTS OF GHRELIN AND ITS ANTAGONIST [D-LYS3]-GHRP-6 ON THE CONDITIONED REACTION OF PLACE PREFERENCE IN ALCOHOLIZED CHRONICALLY RATS
- Authors: Shabanov P.D.1, Morozov V.I.2, Lebedev A.A.2
-
Affiliations:
- S. M. Kirov Military Medical Academy the Russian Defense Ministry
- Institute of Experimental Medicine
- Issue: Vol 35, No 4 (2016)
- Pages: 39-44
- Section: Articles
- Submitted: 10.06.2026
- Published: 31.12.2016
- URL: https://journals.eco-vector.com/RMMArep/article/view/709429
- DOI: https://doi.org/10.17816/rmmar709429
- EDN: https://elibrary.ru/YTMYTU
- ID: 709429
Cite item
Full Text
Abstract
The effects of ghrelin and its antagonist [D-Lys3]-GHRP-6 on the formation, storage and extinction of the conditioned reaction of place preference (CRPP) of ethanol (0.5 g/kg ip) in a 2-chambers apparatus were studied in rats alcoholized with 15% ethanol solution during 6 months. [D-Lys3]-GHRP-6, an antagonist of the ghrelin receptors, administered intranasally in the dose of 10 µg in 20 µl, blocked the CRPP acquisition that was performed by deterioration of staying time in the preferable chamber associated with ethanol by 29.5%. After extinction of CRPP both ghrelin (20 µg in 20 µl intranasally) and [D-Lys3]-GHRP-6 (10 µg in 20 µl) blocked the recovery (or expression) of CRPP of ethanol by 30% in average. It is concluded that ghrelin system participates in the mechanisms of conditioned reinforcement (2 tables, bibliography: 21 refs).
Keywords
About the authors
Petr D. Shabanov
S. M. Kirov Military Medical Academy the Russian Defense Ministry
Author for correspondence.
Saint Petersburg
Vitaliy I. Morozov
Institute of Experimental MedicineSaint Petersburg
Andrey A. Lebedev
Institute of Experimental MedicineSaint Petersburg
References
- Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402: 656-60.
- Chen Ch.-Y., Asakawa A., Fujimiya M., Lee S. D., Inui A. Ghrelin gene products and the regulation of food intake and gut motility. Pharmacol. Rev. 2009; 61: 430-81.
- Howard A. D., Feighner S. D., Cully D. F., Arena J. P., Liberator P. A., Rosenblum C. I., Hamelin M., Hreniuk D. L., Palyha O. C., Anderson J., Paress P. S., Diaz C., Chou M., Liu K. K., McKee K. K., Pong S. S., Chaung L. Y., Elbrecht A., Dashkevicz M., Heavens R., Rigby M., Sirinathsinghji D. J., Dean D. C., Melillo D. G., Patchett A. A., Nargund R., Griffin P. R., DeMartino J. A., Gupta S. K., Schaeffer J. M., Smith R. G., Van der Ploeg L. H. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996; 273 (5277): 974-7.
- Gnanapavan S., Kola B., Bustin S. A., Morris D. G., McGee P., Fairclough P., Bhattacharya S., Carpenter R., Grossman A. B., Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J. Clin. Endocrinol. Metabolism. 2002; 87: 2988.
- Druce M. R., Wren A. M., Park A. J., Milton J. E., Patterson M., Frost G., Ghatei M. A., Small C., Bloom S. R. Ghrelin increases food intake in obese as well as lean subjects. Int. J. Obesity (London). 2005; 29: 1130-6.
- Kroemer N. B., Krebs L., Kobiella A., Grimm O., Pilhatsch M., Bidlingmaier M., Zimmermann U. S., Smolka M. N. Fasting levels of ghrelin covary with the brain response to food pictures. Addict. Biol. 2012; 8: 855-62.
- Holsen L. M., Lawson E. A., Christensen K., Klibanski A., Goldstein J. M. Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa. Psychiatry Res. 2014; 223: 94-103.
- Abizaid A., Liu Z. W., Andrews Z. B., Shanabrough M., Borok E., Elsworth J. D., Roth R. H., Sleeman M. W., Picciotto M. R., Tschöp M. H., Gao X. B., Horvath T. L. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J. Clin. Invest. 2006; 116 (12): 3229.
- Kaur S., Ryabinin A. E. Ghrelin receptor antagonism decreases alcohol consumption and activation of perioculomotor urocortin-containing neurons. Alcoholism Clin. Exp. Res. 2010; 34 (9): 1525-34.
- Gualillo O., Caminos J. E., Nogueiras R., Seoane L. M., Arvat E., Ghigo E., Casanueva F. F., Die´guez C. Effect of food restriction on ghrelin in normal-cycling female rats and in pregnancy. Obesity Res. 2002; 10 (7): 682-7.
- Carroll M. E., France C. P., Meisch R. A. Food-deprivation increases oral and intravenous drug intake in rats. Science. 1979; 205 (4403): 319-21.
- Jerlhag E., Egecioglu E., Dickson S. L., Engel J. A. Glutamatergic regulation of ghrelin-induced activation of the mesolimbic dopamine system. Addict. Biol. 2011; 16 (1): 82-91.
- Patterson Z. R., 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: 632-9.
- Zigman J. M., Jones J. E., Lee C. E., Saper C. B., Elmquist J. K. Expression of ghrelin receptor mRNA in the rat and the mouse brain. J. Comp. Neurol. 2006; 494 (3): 528-48.
- Cabral A., Suescun O., Zigman J. M., Perello M. Ghrelin indirectly activates hypophysiotropic CRF Neurons in rodents. PLoS One. 2012.
- Виноградов П. М., Тиссен И. Ю., Лебедев А. А., Бычков Е. Р., Лавров Н. В., Боткин Е. А., Шабанов П. Д. Антагонист рецепторов грелина [D-Lys3]-GHRP-6 снижает экспрессию условной реакции предпочтения места этанола у крыс. Обзоры по клинической фармакологии и лекарственной терапии. 2015; 13 (2): 27-33.
- Egecioglu E., Jerlhag E., Salome N., Skibicka K. P., Haage D., Bohlooly-Y M., Andersson D., Bjursell M., Perrissoud D., Engel J. A., Dickson S. L. Ghrelin increases intake of rewarding food in rodents. Addict. Biol. 2010; 15 (3): 304-11.
- Perello M., Sakata I., Birnbaum S., Chuang J. C., Osborne-Lawrence S., Rovinsky S. A., Woloszyn J., Yanagisawa M., Lutter M., Zigman J. M. Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol. Psychiatry. 2010; 67 (9): 880-6.
- Cummings D. E. Ghrelin and the short- and long-term regulation of appetite and body weight. Physiol. Behav. 2006; 89: 71-84.
- Dickson S. L., Leng G., Robinson I. C. Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons. Neurosci. 1993; 53: 303-6.
- Lyons A. M., Lowery E. G., Sparta D. R., Thiele T. E. Effects of food availability and administration of orexigenic and anorectic agents on elevated ethanol drinking associated with drinking in the dark procedures. Alcoholism Clin. Exp. Res. 2008; 32 (11): 1962-8.
Supplementary files
