Corticosteroid receptor-mediated mechanisms in the amygdala regulate anxiety and colonic sensitivity.
Our previous studies have shown that stereotaxic implantation of corticosterone (Cort) onto the central amygdaloid nucleus increases both anxiety and colonic sensitivity. The goal of this study was to examine the relative importance of amygdaloid glucocorticoid (GR) and mineralocorticoid receptor (MR)-mediated mechanisms in the induction of anxiety and colonic hypersensitivity. In male Fischer 344 rats, Cort or cholesterol micropellets were stereotaxically implanted bilaterally at the dorsal boundary of the central amygdaloid nucleus either alone or in combination with a GR antagonist, mifepristone, or a MR antagonist, spironolactone. Anxiety was assessed on the elevated plus maze and quantified as the percentage of time spent in open arm exploration. Colonic sensitivity was measured by recording a visceromotor response, the number of abdominal muscle contractions in response to colorectal distension. In Cort-implanted rats there was a significant reduction in the percentage of time spent in the open arms of the elevated plus maze compared with cholesterol controls, indicating increased anxiety. Furthermore, colonic hypersensitivity was observed in response to colorectal distension compared with rats with cholesterol implants. In rats with Cort implants combined with either a GR or MR antagonist, there was a significant inhibition of anxiety and colonic hypersensitivity. Our data suggest that both GR and MR play a critical role in Cort-induced anxiety and colonic hypersensitivity.
Myers
Brent
B
VA Medical Center Research Administration Rm. 151, 921 NE 13St., Oklahoma City, OK 73104, USA.
Greenwood-Van Meerveld
Beverley
B
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D002404:Catheterization; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004343:Drug Implants; D006727:Hormone Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000008:administration & dosage / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D043183:Irritable Bowel Syndrome / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009119:Muscle Contraction; D011312:Pressure; D051381:Rats; D011916:Rats, Inbred F344; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism*; D012677:Sensation / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology
D004343:Drug Implants; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone; D006854:Hydrocortisone