Effects of ghrelin agonist and antagonist on endogenous desacyl-ghrelin content in the brain limbical structures under psychoemotional stress in rats

Abstract

Background. During last years it has been shown the ghrelin signaling system not only regulates energy balance and food intake. It also takes part in reinforcement mechanisms and addiction formation. So the ghrelin system may be considered as possible molecular target to study addiction treatment and post-stressor pharmacological modulation. The aim of this work was to study the effects of ghrelin agonist and antagonist administration on des-acyl ghrelin (DAG) content in the brain structures under stress exposure in Wistar rats. Methods. The acute psychoemotional stress was realized by means of exposure of experimental rats to predator, a tiger python. Ghrelin or ghrelin antagonist D-Lys3-GHRP-6 (Tocris, UK) 10 µg in 20 µl administered intranasally for 7 days after stress exposure. Then brain structures were obtained, homogenized with cryogenic system “Cryomill 200” (Retsch, Germany) and investigated with high-sensitive ELISA (SP-BIO, France). Results. DAG have been detected in every brain structures studied. That are amygdala, hippocampus and hypothalamus. In control group of animals the DAG concentration in hypothalamus was 3-fold more comparning to hippocampus and 2-fold more conparning to amygdala content. The acute stress have dramatically 8-12-fold decrease of DAG concentrations in every brain structures studied. The pharmacological actions on GHSR receptor by ghrelin agonist and antagonist have not affect significant changes in DAG concentrations in every brain structures. Conclusions. The different concentrations of DAG in brain structures in control gtoup supports the view about ghrelin releasing neurons in the hypothalamus. Intranasal administration of ghrelin agonist and antagonist changes the levels of DAG in the hippocampus and the hypothalamus but not in the amygdala nucleus. Our data confirm the opinion about ghrelin-releasing neurons in hypothalamus. The experiments showed the acute stress had caused great depression of ghrelin system in various brain structures. The response of ghrelin system to acute stress occur possibly besides GHSR receptor pathway. The last have been suggested by absence of significant response to ghrelin agonist and antagonist administration.