Background
Parallel lines of research suggest that dysfunction affecting both corticotropin-releasing
factor (CRF) and serotonin (5-HT) systems is involved in the pathophysiology of psychiatric
illnesses such as anxiety and depression. The effect of CRF on behavior and on the
accompanying change in activity of 5-HT neurons in the dorsal and median raphe nuclei
(DR and MR) that project to the ventral medial prefrontal cortex (mPFC), a brain area
implicated in mood and anxiety disorders, was studied.
Methods
Male Sprague-Dawley rats with intra-mPFC deposits of fluorescent microspheres received
injections of CRF (1 μg, intracerebroventricular [ICV]) and were tested for CRF-enhanced
startle, a behavioral assay believed to reflect stress- or anxiety-like states. C-Fos
immunohistochemistry was used to measure CRF-induced activity in retrogradely labeled
neurons in the DR and MR and correlate this level of activity with the level of CRF-enhanced
startle.
Results
The CRF-enhanced startle was accompanied by an increased c-Fos expression in retrogradely
labeled cells in the raphe. In the DR and MR, there was a clear topography of activation,
with a higher-percent activation in retrogradely labeled neurons in caudal sections.
In the caudal DR, this effect was positively correlated with the level of CRF-enhanced
startle. Co-expression of retrogradely labeled cells with tryptophan hydroxylase showed
that the majority (> 90%) of raphe efferents to the mPFC were from serotonergic neurons.
Conclusions
These data indicate that CRF activates a subpopulation of cortical-projecting 5-HT
raphe neurons and suggest that increased 5-HT release in the mPFC might be an important
component driving some types of anxiety-like behaviors.
Key Words
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Article info
Publication history
Published online: December 03, 2007
Accepted:
October 17,
2007
Received in revised form:
September 27,
2007
Received:
June 8,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
