Comparative Study of CRH Microinjections Into PVN and CeA Nuclei on Food Intake, Ghrelin, Leptin, and Glucose Levels in Acute Stressed Rats

Abstract

Introduction: Corticotropin-Releasing Hormone (CRH) is involved in stress and energy homeostasis. On the other hand, CRH receptors also exist within the paraventricular nucleus (PVN) and Central Amygdala (CeA) nuclei. The present study compared the effect of CRH microinjections into PVN and CeA on three consecutive hours and cumulative food intake, internal regulatory factors of food intake, such as serum leptin and ghrelin, as well as blood glucose levels in rats under different acute psychological (Social Stress SS and Isolation Stress IS group) stresses. Methods: Sixty-six male Wistar rats were randomly allocated to 11 groups: Control, Sham, CRH-PVN, CRH-CeA, SS, IS, SS-CRH-PVN, SS-CRH-CeA, IS-CRH-PVN, and IS-CRH-CeA groups. The CRH (2 mu g/kg in 0.5 mu L saline) was injected into PVN and CeA nuclei in rats under everyday, acute social stress and isolation stress conditions. Results: Acute isolation and social stresses did not affect cumulative food intake. Whereas isolation stress led to changes in both leptin and glucose levels, social stress reduced only glucose levels. Cumulative food intake significantly decreased under acute CRH injection into the CeA and particularly into the PVN. Blood glucose significantly reduced in all the groups receiving CRH into their CeA. Conclusion: The PVN played a more important role compared to CeA on food intake. These nuclei probably employ different mechanisms for their effects on food intake. Besides, it seems that exogenously CRH injection into the PVN probably had a more anorectic effect than naturally activated CRH by stresses. Acute isolation stress had a greater impact than social stress on leptin level and cumulative food intake. Thus, elevated food intake related to leptin compared to ghrelin and glucose levels in the CRH-PVN group under acute social stress. Highlights Cumulative food intake reduced in the acute CRH administration into CeA and particularly PVN. The PVN response to food intake emerged earlier than that of CeA. Acute isolation stress had a more destructive effect than social stress on leptin levels. Exogenous CRH into PVN had a greater anorectic effect than endogenous CRH. The CeA is sensitive to glucose changes, the PVN is sensitive to changes in leptin. Plain Language Summary In this study, acute isolation and social stresses did not exhibit any changes in their cumulative food intake probably due to the restricted duration of the induced acute stress. Cumulative food intake reduced in acute CRH injection into the CeA and particularly the PVN. The PVN response to food intake emerged earlier than that of CeA due to more important role of PVN in food intake. Furthermore, leptin level increased only in acute isolation stress with CRH injection into the PVN and CeA, indicating the roles of different circuits in different type of stress. In addition, exogenous CRH into the PVN seemed to have a greater anorectic effect than did naturally activated CRH due to stress induction. Decreased leptin level had a greater influence than ghrelin and glucose on changes food intake in the groups receiving CRH into their PVN and simultaneously subjected to acute social stress than in similar groups subjected to acute isolation stress.