Glucocorticoid receptor-irmnunoreactivity in corticotrophin-releasing factor afferents to the locus coeruleus

The stress-related neurohormone, corticotropin-releasing factor (CRF), also acts as a neurotransmitter to activate the brain noradrenergic nucleus, lo cus coenrleus (LC). Previous electrophysiological findings demonstrating th at tonic CRF secretion in the LC is increased in adrenalectomized rats sugg est that activity of certain CRF afferents to the LC is under inhibitory re gulation by endogenous corticosteroids. The present study was designed to i dentify putative CRF afferents to the LC that may be regulated by glucocort icoids. Retrograde tract tracing from the rat LC and pericoerulear regions was combined with immunohistochemistry to visualize CRF and glucocorticoid receptors in the same sections of rat brain. The retrograde tracer, wheat g erm agglutinin conjugated to horseradish peroxidase coupled to gold (WGA-Au -HRP) was injected into either the nucleus LC or the rostrolateral pericoer ulear region (peri-LC), where CRF-immunoreactive terminals have been demons trated to synapse with LC dendrites. Sections were processed to visualize t he tracer, as well as CRF- and glucocorticoid receptor-immunoreactivity. Fo llowing injections of WGA-Au-HRP into the nuclear LC, triple labeled neuron s were observed primarily in Barrington's nucleus, where 74 +/- 4% of retro gradely labeled CRF-immunoreactive neurons colocalized glucocorticoid recep tor immunoreactivity. In contrast, injections that incorporated the rostrol ateral peri-LC retrogradely labeled numerous neurons that were immunoreacti ve for both CRF and glucocorticoid receptors in the central nucleus of the amygdala. Thus, 94 +/- 2% of the retrogradely labeled CRF-immunoreactive ne urons in the central nucleus of the amygdala colocalized glucocorticoid rec eptor immunoreactivity. Additionally, triple labeled neurons were observed in the bed nucleus of the stria terminalis following WGA-Au-HRP injections that incorporated the rostrolateral peri-LC. The present results implicate Barrington's nucleus, the central nucleus of the amygdala and the bed nucle us of the stria terminalis as glucocorticoid-sensitive sources of CRF that can influence the LC-noradrenergic system. Alterations in glucocorticoid le vels or glucocorticoid receptor function would be predicted to affect the i mpact of these specific CRF systems on LC activity. (C) 1999 Elsevier Scien ce B.V. All rights reserved.