Abstract
Corticotropin-releasing factor (CRF) and related peptides in the central nervous system
appears to have activating properties on behavior and to enhance behavioral responses
to stressors. CRF and urocortin injected into the brain produces increases in arousal
as measured by locomotor activation and increased responsiveness to stressful stimuli.
These effects of CRF appear to be independent of the pituitary adrenal axis and can
be reversed by specific and selective CRF antagonists alpha-helical CRF9–41 and D-Phe CRF12–41. Perhaps more importantly, CRF antagonists can reverse behavioral responses to many
stressors. These results suggest that endogenous CRF systems in the brain may have
a role in mediating behavioral responses to stressors. Norepinephrine systems emanating
from the nucleus locus coeruleus also long have been hypothesized to be involved in
mediating behavioral constructs associated with alertness, arousal, and stress. Pharmacologic,
physiologic, and neuroanatomic evidence supports an important role for a CRF–norepinephrine
interaction in the region of the locus coeruleus in response to stressors that may
be modality- specific where CRF neurons activate the locus coeruleus. One may hypothesize
that another norepinephrine–CRF interaction may occur in the terminal projections
of the forebrain norepinephrine systems in the paraventricular nucleus of the hypothalamus,
the bed nucleus of the stria terminalis, and the central nucleus of the amygdala where
norepinephrine stimulates CRF release. Such a feed-forward system may be particularly
important in situations where an organism must mobilize not only the pituitary adrenal
system but also the central nervous system, in response to environmental challenge.
However, such a feed-forward mechanism in a fundamental brain-activating system may
be particularly vulnerable to dysfunction and thus, may be the key to a variety of
pathophysiologic conditions involving abnormal responses to stressors such as anorexia
nervosa, anxiety, and affective disorders.
Keywords
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Article info
Publication history
Accepted:
June 23,
1999
Received in revised form:
June 4,
1999
Received:
February 24,
1999
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
