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
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.