Alterations in the hypothalamic-pituitary-adrenal axis in a proposed animal model of depression with genetic muscarinic supersensitivity.

Rats from the Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL), which have been bred for differences in sensitivity to cholinergic agonists, were killed by decapitation under quiet, nonstressful conditions and the concentrations of corticotropin-releasing factor (CRF) in various brain regions, the concentrations of CRF receptors in the anterior pituitary, and plasma ACTH and corticosterone concentrations were determined. A first study revealed that the cholinergically hypersensitive FSL rats exhibited lower concentrations of CRF in the median eminence, locus ceruleus, and prefrontal cortex, but no such changes in some 13 other brain regions. In this first study, the FSL rats had significantly lower plasma ACTH concentrations. However, there were no differences in plasma corticosterone concentrations between the two groups. A second study confirmed the results of the first study and revealed that the density of anterior pituitary CRF receptor binding sites was elevated in the FSL rats. The observed pattern of alterations in these measures of HPA axis activity suggest that the cholinergically supersensitive FSL rats may possess diminished HPA activity.