Intracerebroventricular corticotropin-releasing factor increases limbic glucose metabolism and has social context-dependent behavioral effects in nonhuman primates

Elissa M. Strome, G. H Trevor Wheler, J. Dee Higley, Donald (Lynn) Loriaux, Stephen J. Suomi, Doris J. Doudet

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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 μg 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 [18F]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.

Original languageEnglish (US)
Pages (from-to)15749-15754
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number24
DOIs
StatePublished - Nov 26 2002

Fingerprint

Corticotropin-Releasing Hormone
Primates
Glucose
Haplorhini
Anxiety
Anhedonia
Psychomotor Agitation
Fluorodeoxyglucose F18
Major Depressive Disorder
Brain
Pituitary Gland
Amygdala
Neuropeptides
Mood Disorders
Diagnostic and Statistical Manual of Mental Disorders
Positron-Emission Tomography
Antidepressive Agents
Cerebrospinal Fluid
Hippocampus
Central Nervous System

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Intracerebroventricular corticotropin-releasing factor increases limbic glucose metabolism and has social context-dependent behavioral effects in nonhuman primates. / Strome, Elissa M.; Wheler, G. H Trevor; Higley, J. Dee; Loriaux, Donald (Lynn); Suomi, Stephen J.; Doudet, Doris J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 24, 26.11.2002, p. 15749-15754.

Research output: Contribution to journalArticle

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