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Journal of Neuroscience, Vol 13, 3839-3847, Copyright © 1993 by Society for Neuroscience
The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress
D Diorio, V Viau and MJ Meaney
Douglas Hospital Research Center, Department of Psychiatry, Montreal, Canada.
In the studies reported here we have examined the role of the medial
prefrontal cortex (MpFC) in regulating hypothalamic-pituitary-adrenal (HPA)
activity under basal and stressful conditions. In preliminary studies we
characterized corticosteroid receptor binding in the rat MpFC. The results
revealed high-affinity (Kd approximately 1 nM) binding with a moderate
capacity (42.9 +/- 3 fmol/mg) for 3H- aldosterone (with a 50-fold excess of
cold RU28362; mineralocorticoid receptor) and high-affinity (Kd
approximately 0.5-1.0 nM) binding with higher capacity (183.2 +/- 22
fmol/mg) for 3H-RU 28362 (glucocorticoid receptor). Lesions of the MpFC
(cingulate gyrus) significantly increased plasma levels of both
adrenocorticotropin (ACTH) and corticosterone (CORT) in response to a 20
min restraint stress. The same lesions had no effect on hormone levels
following a 2.5 min exposure to ether. Implants of crystalline CORT into
the same region of the MpFC produced a significant decrease in plasma
levels of both ACTH and CORT with restraint stress, but again, there was no
effect with ether stress. Neither MpFC lesions nor CORT implants had any
consistent effect on A.M. or P.M. levels of plasma ACTH or CORT.
Manipulations of MpFC function were not associated with changes in the
clearance rate for CORT or in corticosteroid receptor densities in the
pituitary, hypothalamus, hippocampus, or amygdala. Taken together, these
findings suggest that MpFC is a target site for the negative-feedback
effects of glucocorticoids on stress-induced HPA activity, and that this
effect is dependent upon the nature of the stress.
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