Fast glucocorticoid negative feedback is an intriguing phenomenon, the mechanisms of which have yet to be clearly established. Furthermore, the connection between glucocorticoid feedback and sucrose consumption following stress has been an interest of the Dallman Lab for decades. The experiments proposed in this grant attempt to further increase our understanding of the link between HPA function and ingestive behaviors, focusing on endocannabinoid actions as an intermediary. Preliminary data collected in our laboratory shows that injection of the specific glucocorticoid receptor (GR) agonist RU28362 2min before the onset of restraint stress rapidly suppresses stress-induced ACTH secretion. Furthermore, recent studies by Di et al. have shown that endocannabinoids (eCBs) are able to modulate HPA function via a GR modulated retrograde signal from the paraventricular nucleus that blocks glutamate transmission, supporting our further preliminary studies which show that endocannabinoid antagonists not only alter HPA negative feedback, but suppress sucrose consumption following glucocorticoid treatment. The proposed experiments will allow us to observe closely examine the role of endocannabinoids in HPA regulation, from gene expression to hormone secretion, and observe the further metabolic consequences of these actions. Specifically, we propose to (1) further explore the fast feedback phenomenon already shown in our preliminary data with an extended time course.
| Ginsberg, Abigail B; Pecoraro, Norman C; Warne, James P et al. (2010) Rapid alteration of stress-induced hypothalamic-pituitary-adrenal hormone secretion in the rat: a comparison of glucocorticoids and cannabinoids. Stress 13:248-57 |
| Warne, James P; Akana, Susan F; Ginsberg, Abigail B et al. (2009) Disengaging insulin from corticosterone: roles of each on energy intake and disposition. Am J Physiol Regul Integr Comp Physiol 296:R1366-75 |
| Foster, Michelle T; Warne, James P; Ginsberg, Abigail B et al. (2009) Palatable foods, stress, and energy stores sculpt corticotropin-releasing factor, adrenocorticotropin, and corticosterone concentrations after restraint. Endocrinology 150:2325-33 |
