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The Journal of Neuroscience, June 15, 1999, 19(12):5016-5025
Modulation of Learning and Anxiety by Corticotropin-Releasing
Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2
Jelena
Radulovic,
Andreas
Rühmann,
Thomas
Liepold, and
Joachim
Spiess
Max Planck Institute for Experimental Medicine, Department for
Molecular Neuroendocrinology, 37075 Goettingen, Germany
The differential modulation of learning and anxiety by
corticotropin-releasing factor (CRF) through CRF receptor subtypes 1 (CRFR1) and 2 (CRFR2) is demonstrated. As learning paradigm, context-
and tone-dependent fear conditioning of the mouse was used. Injection
of CRF into the dorsal hippocampus before training enhanced
learning through CRFR1 as demonstrated by the finding that this effect
was prevented by the local injection of the unselective CRFR antagonist
astressin, but not by the CRFR2-specific antagonist antisauvagine-30
(anti-Svg-30). In contrast, injection of CRF into the lateral
intermediate septum impaired learning through CRFR2, as demonstrated by
the ability of antisauvagine-30 to block this effect. When
antisauvagine-30 was injected alone into the lateral intermediate
septum, learning was enhanced. Such tonic control of learning was not
observed when astressin or antisauvagine-30 was injected into the
dorsal hippocampus. Injection of CRF after the training into the dorsal
hippocampus and the lateral intermediate septum also enhanced and
impaired learning, respectively. Thus, it was indicated that CRF acted
on memory consolidation. It was concluded that the observed effects
reflected changes of associative learning and not arousal, attention,
or motivation. Although a dose of 20 pmol human/rat CRF was sufficient
to affect learning significantly, a fivefold higher dose was required
to induce anxiety by injection into the septum. Immobilization for 1 hr
generated a stress response that included the induction of anxiety
through septal CRFR2 and the subsequent enhancement of learning through hippocampal CRFR1. The involvement of either receptor subtype was
demonstrated by region-specific injections of astressin and antisauvagine-30.
Key words:
CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
Copyright © 1999 Society for Neuroscience 0270-6474/99/19125016-10$05.00/0
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[Abstract]
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8515 - 8527.
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799 - 806.
[Abstract]
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