Open Access[D-Lys 3]-GHRP-6, an antagonist of ghrelin receptors, decreases expression of conditioned place preference reaction of ethanol in rats
Author(s) -
Petr Mikhailovich Vinogradov,
Ilya Yurievich Tissen,
А. А. Лебедев,
Eugenii R. Bychkov,
Nikanor V. Lavrov,
Eugeny Alexandrovich Botkin,
Petr Dmitriyevich Shabanov
Publication year - 2015
Publication title -
obzory po kliničeskoj farmakologii i lekarstvennoj terapii
Language(s) - English
Resource type - Journals
eISSN - 2542-1875
pISSN - 1683-4100
DOI - 10.17816/rcf13227-33
Subject(s) - ghrelin , antagonist , ethanol , conditioned place preference , alcohol , receptor , endocrinology , receptor antagonist , chemistry , medicine , extinction (optical mineralogy) , self administration , pharmacology , biochemistry , mineralogy
Ghrelin is a peptide hormone synthesized and secreted by the stomach into the bloodstream. The greatest attention of neuroscience research is devoted to investigation of acylated form of ghrelin, which is a specific ligand for the receptor subcortical nuclei of the brain. The aim of this study was to analyze the action of ghrelin and its antagonist on the expression of conditioned place preference (СPP) of ethanol. To develop CPP of alcohol we used a two-chamber apparatus. Rats were spent 74 % of time experiment in chamber associated with alcohol. Rats receiving intranasal receptor ghrelin antagonist [D-Lys3]-GHRP-6 (10 µg) reduced the time of staying in the chamber associated with alcohol for 46 % (p < 0.05). Rats treated with intranasal ghrelin spent in the chamber, associated with alcohol, for 60 % of time. Then the extinction of CPP was produced when rats was replaced into the apparatus every day for 7 days without administration alcohol or any substances. On the 7th day of extinction, CPP was not reproduced. But after administration of ethanol on the 7th day CPP was reinstated. Animals received GHS-R1A receptor ghrelin antagonist [D-Lys3]-GHRP-6 (10 µg) and ethanol spent 50 % of time in chamber associated with the administration of ethanol, i.e. CPP was not reinstated. Animals treated with ghrelin, demonstrated a range of reactions from a sharp preference to avoidance of the place associated with ethanol. Thus, the present study shows the important role of ghrelin in the mechanisms of the reinforcing effects of alcohol and demonstrates the prospect for using of ghrelin antagonists in the correction of pathological craving in addictive disordes.