Decreased CCK(B) receptor binding in rat amygdala in animals demonstrating greater anxiety-like behavior.
BACKGROUND
The potentiation of the acoustic startle response (ASR) by stimuli associated with aversive events is mediated via the amygdala and is used as an index of "anxiety" and "fear". In laboratory animals, cholecystokinin(B) (CCK(B)) agonists increase anxiety and fear and activation of amygdala CCK(B) receptors potentiates ASR. Additionally, antagonism of CCK(B) receptors attenuates fear-potentiated ASR.


OBJECTIVE
To investigate the putative role of CCK(B) receptors in individual differences in fear and anxiety, we examined individual differences in amygdala CCK(B) receptor binding for animals demonstrating low versus high baseline and fear-potentiated ASR. Additionally, we examined individual differences in CCK(B) binding for animals demonstrating low versus high anxiety-like behavior on the elevated plus-maze (EPM).


METHODS
Male Wistar rats were tested in the ASR, fear-potentiated ASR, and EPM paradigms. Following testing, brain slices were mounted and incubated with 50 pM (125)I-CCK8 (non-sulfated), a selective CCK(B) receptor ligand, in the presence or absence of 1 micro M non-radioactively labeled CCK and then exposed on tritium-sensitive film for 2-3 days.


RESULTS
Animals with high fear-potentiated ASR showed decreased CCK(B) receptor binding in both the basolateral and central amygdaloid nuclei. Animals with high anxiety-like responses on the EPM showed decreased CCK(B) binding in the basolateral, but not central, amygdala. There were no differences in amygdala CCK(B) binding in animals demonstrating low versus high baseline ASR. None of the groups showed differences in CCK(B) receptor binding in the nucleus accumbens.


CONCLUSIONS
These results show that there is a down-regulation of amygdala CCK(B) receptor binding in animals demonstrating greater anxiety-like responding in the fear-potentiated ASR and EPM models of anxiety, possibly as a compensation for increased CCK activity.
Wunderlich
Glen R
GR
Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 3G3.
Raymond
Roger
R
DeSousa
Norberto J
NJ
Nobrega
José N
JN
Vaccarino
Franco J
FJ
D000161:Acoustic Stimulation; D000679:Amygdala / Q000378:metabolism* / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D002766:Cholecystokinin / Q000378:metabolism; D003214:Conditioning, Classical; D005239:Fear / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000378:metabolism* / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology
D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin