Neurochemical mechanisms and pharmacology of ghrelins

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Abstract

The purpose of the review was to analyze the neurochemical and neurophysiological mechanisms of the ghrelin system and the role of ghrelin in body functions and behavior. The focus is on the participation of ghrelin in the mechanisms of reinforcement and the formation of addictive behavior. At the beginning of the review a history of the first works on the field of ghrelin and its receptor was described. Then, genetic control, molecular precursor of ghrelin, molecular forms of ghrelin and ghrelin receptor were represented. In particular, the distribution of the ghrelin receptor, ghrelin-producing cells in the brain and its participation in various physiological functions of the body were shown. The hypothalamic functions of ghrelin were discussed: energy balance, regulation of glucose metabolism, stimulation of eating behavior, regulation of hypophys-pituitary axis (HPA) system. The connection of ghrelin with the brain CRH system was demonstrated. In particular, activation of HPA was described as a possible mechanism through which ghrelin regulates a number of physiological processes. Extrahypothalamic action of ghrelin was shown on the basis of the mechanisms of reinforcement and addiction. On the basis of their own data and literary, it was concluded that action of alcohol and psychoactive drugs are reduced after the ghrelin receptors blockade. In particular, it has been demonstrated that alcoholization of mothers affects the activity of the ghrelin system during the prenatal and early postnatal periods of development in the offspring of rats. It was shown the participation of ghrelin in memory and learning. The further perspective of the study and practical application of ghrelin-based pharmacological agents was analyzed.

About the authors

Petr D. Shabanov

Institute of Experimental Medicine; S.M. Kirov Military Medical Academy

Author for correspondence.
Email: pdshabanov@mail.ru

Dr. Med. Sci. (Pharmacology), Professor and Head, Dept. of Neuropharmacology; Head, Department of Pharmacology

Russian Federation, Saint Petersburg

Andrei A. Lebedev

Institute of Experimental Medicine

Email: aalebedev-iem@rambler.ru

Dr. Biol. Sci. (Pharmacology), Head of the Laboratory of General Pharmacology, Dept. of Neuropharmacology

Russian Federation, Saint Petersburg

Eugenii R. Bychkov

Institute of Experimental Medicine

Email: bychkov@mail.ru

PhD (Pathophysiology), Head of the Laboratory of Chemistry and Pharmacology of Medicinal Compounds, Dept. of Neuropharmacology

Russian Federation, Saint Petersburg

Nikanor V. Lavrov

St. Petersburg State Pediatric Medical University

Email: nikanlavr@rambler.ru

PhD (Pharmacology), Assistant Professor, Dept. оf Pharmacology

Russian Federation, Saint Petersburg

Vitalii I. Morozov

Institute of Experimental Medicine

Email: vitmoroz@yandex.ru

PhD (Narcology), Postdoc Student, Dept. of Neuropharmacology

Russian Federation, Saint Petersburg

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