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Journal of Neuroscience, Vol 10, 176-183, Copyright © 1990 by Society for Neuroscience
Corticotropin-releasing factor produces fear-enhancing and behavioral activating effects following infusion into the locus coeruleus
PD Butler, JM Weiss, JC Stout and CB Nemeroff
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710.
The present series of experiments tested the hypothesis that the behavioral
activating and anxiogenic effects produced by intraventricular
administration of corticotropin-releasing factor (CRF) may be mediated by
noradrenergic neurons in the brain-stem locus coeruleus (LC). Results
showed that infusion of CRF into the LC (100 ng) significantly increased
nonambulatory spontaneous motor activity measured in photocell cages;
ambulatory (i.e., locomotor) activity was not altered. In the modified
Porsolt swim test, which examines arousal and agitation in a stressful
situation, significant behavioral activation (i.e., decreased floating) was
seen following infusion of CRF (10 ng) into the LC; a 500 ng dose of CRF
was necessary to produce similar effects following infusion into the
lateral ventricle. The results of these 2 tests suggest that the behavioral
activating effects of CRF in the LC may be related to arousing or
stress-related effects, rather than to increased locomotor activity per se.
Anxiogenic activity was assessed in animals placed in an open field
containing a small, darkened compartment. Infusion or CRF into the LC
(1-100 ng) significantly increased the time spent in the compartment and
decreased the amount of time spent exploring the outside of the compartment
or venturing into the inner squares of the open field, all indices of
anxiogenic behavior. Biochemical studies showed that bilateral infusion of
CRF into the LC produced significant increases in the concentration of the
norepinephrine metabolite 3,4-dihydroxyphenylglycol in such forebrain
projection areas of the LC as the amygdala and posterior hypothalamus.
These data, taken together, suggest that CRF produces its behavioral
activating and anxiogenic effects, at least in part, by increasing the
activity of LC noradrenergic neurons.
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