Glucocorticoid receptor blockade in the dorsal hindbrain attenuates body weight gain in response to chronic restraint stress

Abstract

Chronic stress can elevate endogenous glucocorticoid levels. The current experiments were performed to test the hypothesis that dorsal hindbrain (DHB) glucocorticoid receptors (GRs) contribute to the effects of glucocorticoids on responses to chronic restraint stress. Small pellets of the GR antagonist Mifepristone (Mif) or silastic (sham pellet) were implanted on the DHB of adult male borderline hypertensive rats (BHRs). Rats were then subjected to chronic daily restraint stress by placing each rat in a clear Plexiglas tube for either 1 hour (h)/day (d) for 14 d or 2 h/d for 26 d, on most days. Two additional non-stressed control groups (DHB sham and DHB Mif) were weighed daily for 14 d. On day 10 or 22 of treatment, indwelling arterial catheters were implanted to measure baseline mean arterial pressure (MAP) and heart rate (HR). In DHB sham-treated rats, chronic restraint stress tended to increase body weight gain, with this effect reaching significance on day 7 (P=0.03) of treatment. DHB Mif treatment reduced body weight gain during chronic stress (P<0.01 for both restraint protocols). For example, on day 7 of treatment weight gain in chronically stressed rats (1 h/d) was 31 ± 3 g in DHB sham rats and 1 ± 6 g in DHB Mif rats, while unstressed DHB sham and DHB Mif rats gained 16 ± 4 g and 17 ± 4 g, respectively. Baseline MAP was not significantly reduced by DHB Mif. However, in the chronically stressed rats HR was decreased in the DHB Mif (305 ± 2 bpm, P<0.01) relative to the DHB sham group (HR=348 ± 8 bpm). We conclude that blockade of DHB GRs attenuates weight gain in chronically stressed BHRs. Supported by NIH Grant HL-076807