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 microg, intracerebroventricular [i.c.v.]) 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.
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 microg, intracerebroventricular [i.c.v.]) 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.
Authors: T M Reyes; K Lewis; M H Perrin; K S Kunitake; J Vaughan; C A Arias; J B Hogenesch; J Gulyas; J Rivier; W W Vale; P E Sawchenko Journal: Proc Natl Acad Sci U S A Date: 2001-02-27 Impact factor: 11.205
Authors: Ross A McDevitt; Ryoko Hiroi; Scott M Mackenzie; Nicholas C Robin; Aaron Cohn; Jeansok J Kim; John F Neumaier Journal: Biol Psychiatry Date: 2011-02-26 Impact factor: 13.382