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Corticotropin-releasing factor, norepinephrine, and stress
1Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Biological Psychiatry
|November 24, 1999
Summary
Central nervous system corticotropin-releasing factor (CRF) activates behavior and stress responses. CRF antagonists reverse these effects, suggesting endogenous CRF systems mediate stress responses and may be implicated in disorders like anxiety.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Neuroendocrinology
Background:
- Corticotropin-releasing factor (CRF) and related peptides in the central nervous system (CNS) exhibit activating properties on behavior.
- CRF and urocortin administration into the brain increases arousal, locomotor activity, and responsiveness to stressors.
- These CNS effects of CRF are independent of the pituitary adrenal axis.
Purpose of the Study:
- To investigate the role of endogenous CRF systems in mediating behavioral responses to stressors.
- To explore the interaction between CRF and norepinephrine systems in stress response pathways.
- To understand the potential involvement of CRF-norepinephrine interactions in the pathophysiology of stress-related disorders.
Main Methods:
- Administration of CRF and urocortin into the brain to measure behavioral changes.
- Utilized specific CRF antagonists (alpha-helical CRF9-41 and D-Phe CRF12-41) to reverse CRF-induced effects.
- Examined neuroanatomic and physiological evidence for CRF-norepinephrine interactions in key brain regions like the locus coeruleus, hypothalamus, and amygdala.
Main Results:
- Central administration of CRF and urocortin increased arousal and behavioral responses to stressors.
- CRF antagonist administration reversed CRF-induced behavioral activation and stress responses.
- Evidence supports a CRF-norepinephrine interaction in the locus coeruleus, where CRF activates norepinephrine neurons, and in forebrain projections, where norepinephrine stimulates CRF release.
Conclusions:
- Endogenous CRF systems in the brain play a significant role in mediating behavioral responses to stressors.
- A CRF-norepinephrine feed-forward system in the CNS is proposed, crucial for mobilizing behavioral and physiological responses to environmental challenges.
- Dysfunction in this fundamental brain-activating system may underlie pathophysiological conditions such as anorexia nervosa, anxiety, and affective disorders.