Systems Neurobiology Laboratory, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
Integrative Laboratory of Cardiovascular and Neurological Pathophysiology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
Behav Brain Res. 2019 Jun 3;365:178-184. doi: 10.1016/j.bbr.2019.03.017. Epub 2019 Mar 8.
Ghrelin is a recently discovered peptide, mainly produced in the stomach and involved in body's energy-maintenance processes. Ghrelin exerts its actions by activating the growth hormone secretagogue receptor (GHS-R). Recent analyses indicate that ghrelin targets the brain to regulate a wealth of functions, including behavioral responses that have been associated with stress and anxiety mechanisms. In this context, evidence shows the presence of GHS-R receptors in the dorsal raphe nucleus (DRN), the main source of serotonergic neurons that innervate encephalic structures involved in emotional control. Our study aims to evaluate the effects of the pharmacological manipulation of ghrelin receptors located in the DRN on the expression of the behavioral responses of Wistar rats. Such responses were assessed in the elevated T maze (ETM), an experimental model that allows the measurement, in the same animal, of two defensive tasks, inhibitory avoidance and escape. Our results showed that the intra-DRN infusion of ghrelin impaired the acquisition of inhibitory avoidance, an anxiolytic-like effect, and facilitated the expression of escape response in the ETM, indicating a panicogenic-like effect. The intra-DRN administration of the ghrelin receptor (GHS-R1a) antagonist PF-04628935 did not alter the behavioral tasks assessed in the ETM. Finally, our results revealed that intra-DRN infusions of PF-04628935 prior to the administration of ghrelin into this area neutralized the behavioral effects obtained in the ETM. Taken together, our data reveal the involvement of DRN GHS-R1a receptors in the regulation of defensive tasks that have been associated with generalized anxiety and panic disorders.
胃饥饿素是一种新发现的肽类物质，主要在胃中产生，参与机体的能量维持过程。胃饥饿素通过激活生长激素促分泌受体（GHS-R）发挥作用。最近的分析表明，胃饥饿素作用于大脑以调节大量功能，包括与应激和焦虑机制相关的行为反应。在这种情况下，有证据表明生长激素促分泌受体（GHS-R）存在于中缝背核（DRN），DRN 是支配大脑中与情绪控制相关结构的 5-羟色胺能神经元的主要来源。我们的研究旨在评估 DRN 中胃饥饿素受体的药理学操纵对 Wistar 大鼠行为反应表达的影响。这些反应在高架 T 迷宫（ETM）中进行评估，ETM 是一种实验模型，允许在同一动物中测量两种防御任务，即抑制性回避和逃避。我们的结果表明，DRN 内注射胃饥饿素会损害抑制性回避的获得，产生抗焦虑样作用，并促进 ETM 中逃避反应的表达，表明具有惊恐样作用。DRN 内给予胃饥饿素受体（GHS-R1a）拮抗剂 PF-04628935 不会改变 ETM 中评估的行为任务。最后，我们的结果表明，DRN 内注射 PF-04628935 可中和胃饥饿素在该区域内注射对 ETM 中获得的行为影响。总之，我们的数据表明，DRN GHS-R1a 受体参与调节与广泛性焦虑和惊恐障碍相关的防御任务。
