Influência dos receptores GHS-R1a nas respostas comportamentais e térmicas diante da endotoxemia

Abstract

Endotoxemia is an appropriate model to study the immune response against bacterial invasion. The administration of this toxin triggers a rapid immune response that culminates in the release of proinflammatory cytokines and hormones, such as corticosterone. Along with others, these mediators are responsible for the expression of a sick phenotype in animals. This phenotype involves behavioral changes that together are called sickness behavior. Modulating agents of the inflammatory response are capable of generating significant changes in this type of behavior. Ghrelin is an orexigenic hormone mainly synthesized in the stomach that presents wide performance in several tissues and therefore, is considered a multifunctional hormone. Among its already recognized functions, we can mention its immunomodulatory and activator effect on the hypothalamic‐pituitary‐adrenal axis. Therefore, the objective of the present study was to evaluate, in male Wistar rats, the influence of intracerebroventricular administration of ghrelin receptors antagonist over sickness behavior, thermoregulatory responses and HPA axis activation in endotoxic animals. For this purpose, these were submitted to the tests of open field, sucrose preference, food intake and social interaction, and had the serum corticosterone levels measured as well as the body temperature monitored. Prior to the study of Ghrelin effects on sickness behavior, a study was conducted to establish the best dose and the best post-treatment time to perform the test. The results of this first part of the work demonstrated that the three doses tested (200, 500 and 1000μg/Kg) are capable to evoke the sickness behavior, that shows itself more evident 2 hours after endotoxemia induction. The results of the second part of the work demonstrated that the central infusion of ghrelin receptors antagonist reduces expression of sickness behavior, as it improves all behavioral responses of animals against LPS. Use of the antagonist was also able to reduce serum corticosterone levels. However, body temperature monitoring results showed that pre-treatment with [DLys3] -GHRP-6 is not capable of modifying the febrile response due endotoxemia. Therefore, we conclude that ghrelin receptors antagonist plays a key modulatory effect on sickness behavior, but can not alter the febrile response evoked by LPS treatment.