Intracerebroventricular corticotropin-releasing factor increases limbic glucose metabolism and has social context-dependent behavioral effects in nonhuman primates.
Corticotropin-releasing factor (CRF) is a neuropeptide involved in integrating the behavioral, autonomic, and hormonal responses to stress within the central nervous system. Patients suffering from depression have abnormal activity in stress responsive brain regions and elevated cerebrospinal fluid CRF. The DSM-IV criteria for major depressive disorder include behavioral changes such as depressed mood, anhedonia, and psychomotor agitation/retardation. We studied the effects of 434 microgram of CRF given intracerebroventricularly over 40 min in group and individually housed monkeys to examine the role of elevated levels of central CRF on behavior. CRF elicited a wide range of behaviors, which fell into three broad categories: anxiety-like, depressive-like, and externally oriented. Externally oriented behaviors decreased, and anxiety-like behaviors increased regardless of how the animals were housed. Interestingly, increased depressive-like behaviors were only observed when the animals were socially housed. In a separate experiment, we examined the effects of the same dose of CRF on the regional cerebral glucose metabolism of lightly anesthetized monkeys by using positron emission tomography and [(18)F]fluorodeoxyglucose. CRF infusion increased glucose metabolism in the pituitary/infundibulum, the amygdala, and hippocampus. These results indicate that increased central CRF tone affects primate behavior in a context-dependent manner, and that it activates limbic and stress-responsive regions. The fact that intracerebroventricular CRF increases depressive-like behavior in socially housed animals and increases activity in limbic brain regions may help explain the behavioral and metabolic alterations in humans with affective disorders, and this model could therefore have significant value in the development of novel antidepressant treatments.
Strome
Elissa M
EM
Pacific Parkinson's Research Center and Department of Medicine, University of British Columbia, Vancouver, Canada V6T 2B5. strome@interchange.ubc.ca
Wheler
G H Trevor
GH
Higley
J Dee
JD
Loriaux
D Lynn
DL
Suomi
Stephen J
SJ
Doudet
Doris J
DJ
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001786:Blood Glucose / Q000032:analysis; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D003863:Depression / Q000139:chemically induced*; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006799:Housing, Animal; D006854:Hydrocortisone / Q000097:blood; D007276:Injections, Intraventricular; D008032:Limbic System / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D023421:Models, Animal; D019964:Mood Disorders / Q000503:physiopathology; D010902:Pituitary Gland / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D016037:Single-Blind Method; D012919:Social Behavior; D012934:Social Isolation; D014055:Tomography, Emission-Computed
D001786:Blood Glucose; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D005947:Glucose; D006854:Hydrocortisone