Differential involvement of amygdala corticosteroid receptors in visceral hyperalgesia following acute or repeated stress

Am J Physiol Gastrointest Liver Physiol. 2012 Jan 15;302(2):G260-6. doi: 10.1152/ajpgi.00353.2011. Epub 2011 Nov 3.


Symptoms of irritable bowel syndrome (IBS) are exacerbated by stress. Previously, we demonstrated that the stress hormone corticosterone applied directly to the amygdala induced visceral hypersensitivity through the actions of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). However, the involvement of amygdaloid GR and MR in the regulation of visceral sensitivity following psychological stress is unknown; therefore, the goal of the present study was to determine the relative importance of amygdaloid GR and MR in the regulation of visceral sensitivity in a rodent model of behavioral stress. Male F-344 rats were stereotaxically implanted with micropellets bilaterally on the dorsal margin of the amygdala containing the GR antagonist mifepristone, the MR antagonist spironolactone, or cholesterol as a control. Animals were then exposed to 1 h of water-avoidance stress (WAS) or sham stress for 1 day (acute) or 7 days (repeated). Visceral sensitivity was assessed either 1 h or 24 h after the final session of WAS and quantified as the number of contractions of the external abdominal oblique, a visceromotor response, in response to colorectal distension at pressures of 0-60 mmHg. Acute stress induced transient visceral hyperalgesia, which was absent 24 h after WAS and independent of GR and MR. Conversely, repeated WAS induced sustained visceral hyperalgesia that was abolished by specifically targeting the amygdala with GR and MR antagonists. These results demonstrate that the amygdala corticosteroid system plays an essential role in mediating the effects of repeated WAS on visceral sensitivity. Furthermore, our findings suggest that amygdaloid GR and MR may be involved in IBS symptomatology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Animals
  • Colon / metabolism
  • Hormone Antagonists / pharmacology
  • Hyperalgesia / metabolism*
  • Irritable Bowel Syndrome / metabolism
  • Male
  • Mifepristone / pharmacology
  • Rats
  • Rats, Inbred F344
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Mineralocorticoid / metabolism*
  • Spironolactone / pharmacology
  • Stress, Psychological / metabolism*


  • Hormone Antagonists
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • Spironolactone
  • Mifepristone