Increased corticotropin-releasing factor concentrations in the bed nucleus of the stria terminalis of anhedonic rats.
Chronic mild stress in rats is an antidepressant-responsive model for anhedonic symptoms of major depression. Many patients with depression exhibit alterations in hypothalamic-pituitary-adrenal axis activity, and corticotropin-releasing factor (CRF) neuronal function. This study investigated the potential involvement of CRF and CRF receptors in the development of chronic mild stress-induced anhedonia in rats. Rats were subjected to 19 days of chronic mild stress, during which time anhedonia was periodically assessed by determining the threshold for self-stimulation of the ventral tegmental area. Anhedonic rats exhibited a 50% increase in CRF concentrations in the bed nucleus of the stria terminalis compared to control rats. There were no significant changes in hypothalamic-pituitary-adrenal axis activity, CRF or CRF(1) receptor mRNA expression, or CRF receptor binding in the brain regions analyzed. Though preliminary, these results are consistent with the hypothesis that chronic stress-induced modulation of CRF function in specific brain structures such as the bed nucleus of the stria terminalis may contribute to the pathophysiology of depression.
Stout
S C
SC
Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000, 30322, Atlanta, GA, USA.
Mortas
P
P
Owens
M J
MJ
Nemeroff
C B
CB
Moreau
J
J
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001667:Binding, Competitive; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D003866:Depressive Disorder / Q000503:physiopathology*; D015870:Gene Expression; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D012686:Septal Nuclei / Q000378:metabolism*; D013312:Stress, Physiological / Q000503:physiopathology
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone