Modulation of learning and anxiety by corticotropin-releasing factor (CRF)and stress: Differential roles of CRF receptors 1 and 2

Citation
J. Radulovic et al., Modulation of learning and anxiety by corticotropin-releasing factor (CRF)and stress: Differential roles of CRF receptors 1 and 2, J NEUROSC, 19(12), 1999, pp. 5016-5025
Citations number
52
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
02706474 → ACNP
Volume
19
Issue
12
Year of publication
1999
Pages
5016 - 5025
Database
ISI
SICI code
0270-6474(19990615)19:12<5016:MOLAAB>2.0.ZU;2-7
Abstract
The differential modulation of learning and anxiety by corticotropin-releas ing factor (CRF) through CRF receptor subtypes 1 (CRFRI) and 2 (CRFR2) is d emonstrated. As learning paradigm, context- and tone-dependent fear conditi oning of the mouse was used. Injection of CRF into the dorsal hippocampus b efore training enhanced learning through CRFR1 as demonstrated by the findi ng that this effect was prevented by the local injection of the unselective CRFR antagonist astressin, but not by the CRFR2-specific antagonist antisa uvagine-30 (anti-Svg-30). In contrast, injection of CRF into the lateral in termediate septum impaired learning through CRFR2, as demonstrated by the a bility 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 antisauv agine-30 was injected into the dorsal hippocampus. Injection of CRF after t he 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, attentio n, or motivation. Although a dose of 20 pmol human/rat CRF was sufficient t o affect learning significantly, a fivefold higher dose was required to ind uce anxiety by injection into the septum. Immobilization for 1 hr generated a stress response that included the induction of anxiety through septal CR FR2 and the subsequent enhancement of learning through hippocampal CRFR1. T he involvement of either receptor subtype was demonstrated by region-specif ic injections of astressin and antisauvagine-30.