Irritable bowel syndrome (IBS) symptoms are due in part to alterations in visceral sensation. IBS symptoms are frequently exacerbated by stress and anxiety, which suggests a link between cognitive and peripheral autonomic activity. The amygdala has been implicated as a key limbic structure involved in anxiety and activation of the hypothalamic-pituitary-adrenocortical axis. It has been demonstrated that administration of glucocorticoids in the area of the amygdala increases anxiety in rats. Furthermore, rats genetically predisposed to heightened levels of anxiety display a hypersensitive response to colonic distention. The PI hypothesizes that manipulation of amygdala function by glucocorticoids induces colonic hypersensitivity through modulation of spinal neuronal activity. The PI proposes to modulate anxiety by manipulating amygdala function directly with corticosterone and specific glucocorticoid antagonists to determine mechanisms by which the CNS regulates visceral sensitivity. Visceromotor reflexes in response to colorectal distention will be used to determine visceral hypersensitivity in rats with normal and """"""""hypersensitive"""""""" colons. It is proposed that chronic stress resulting in elevated glucocorticoid levels could, through the amygdala, modulate the function of critical spinal neurons involved in the colonic stimuli. To further explore the mechanisms involved the PI will modulate amygdala function with glucocorticoids and its effect on spinal cord neuronal activity. Recordings will be made from rat lumbosacral spinal nerves in response to colonic distention following treatment with corticosterone or specific antagonists delivered to the amygdala. This R21 proposal will develop collaborations among scientists in GI neurophysiology, pharmacology, and neuroendocrinology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK057028-01A1
Application #
6200173
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Hamilton, Frank A
Project Start
2000-09-30
Project End
2002-08-31
Budget Start
2000-09-30
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$119,359
Indirect Cost
Name
Oklahoma Foundation for Digestive Research
Department
Type
DUNS #
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Myers, Brent; Dittmeyer, Kale; Greenwood-Van Meerveld, Beverley (2007) Involvement of amygdaloid corticosterone in altered visceral and somatic sensation. Behav Brain Res 181:163-7
Greenwood-Van Meerveld, Beverley; Johnson, Anthony C; Schulkin, Jay et al. (2006) Long-term expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus in response to an acute colonic inflammation. Brain Res 1071:91-6
Qin, Chao; Foreman, Robert D (2004) Viscerovisceral convergence of urinary bladder and colorectal inputs to lumbosacral spinal neurons in rats. Neuroreport 15:467-71
Qin, Chao; Greenwood-Van Meerveld, Beverley; Foreman, Robert D (2003) Spinal neuronal responses to urinary bladder stimulation in rats with corticosterone or aldosterone onto the amygdala. J Neurophysiol 90:2180-9
Qin, Chao; Greenwood-Van Meerveld, Beverley; Foreman, Robert D (2003) Visceromotor and spinal neuronal responses to colorectal distension in rats with aldosterone onto the amygdala. J Neurophysiol 90:2-11