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Journal of Neuroscience, Vol 15, 5439-5447, Copyright © 1995 by Society for Neuroscience
Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis
EM Pich, M Lorang, M Yeganeh, F Rodriguez de Fonseca, J Raber, GF Koob and F Weiss
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Previous research has suggested a role for corticotropin-releasing factor
(CRF) in the anxiogenic effects of stressful stimuli and ethanol
withdrawal. This hypothesis was explored in a series of experiments using
intracranial microdialysis to monitor CRF-like immunoreactivity (CRF-IR) in
the extracellular compartment of the rat amygdala. The synaptic origin of
CRF-IR release in the amygdala was determined in vitro by assessing the
Ca2+ dependency of 4-aminopyridine stimulated CRF-IR release from tissue
preparations of rat amygdala. In vivo experiments were performed in awake
rats after the placement of microdialysis probes in the amygdala. In the
first experiment, transient restraint stress (20 min) produced an increase
of CRF-IR release (basal levels, 1.19 +/- 0.15 fmol/50 microliters; stress
levels, 4.54 +/- 1.33 fmol/50 microliters; p < 0.05) that returned to
basal values within 1 hr. When 4-aminopyridine (5 mM) was added to the
perfusion medium, it consistently increased CRF-IR release (4.83 +/- 0.92
fmol/50 microliters, p < 0.05). In the second experiment, CRF-IR release
was measured during ethanol withdrawal in rats previously maintained for
2-3 weeks on a liquid diet containing ethanol (8.5%). Basal CRF-IR levels
were 2.10 +/- 0.43 fmol/50 microliters in ethanol exposed rats and 1.30 +/-
0.19 fmol/50 microliters in control rats. During withdrawal, a progressive
increase of CRF-IR levels over time was observed, reaching peak values at
10-12 hr after the onset of withdrawal (10.65 +/- 0.49 fmol/50 microliters
vs 1.15 +/- 0.30 fmol/50 microliters of control rats, p <
0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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