Altered amygdalar CRF release and increased anxiety-like behavior in Sardinian alcohol-preferring rats: a microdialysis and behavioral study.
BACKGROUND
Dysregulation of the stress-regulatory corticotropin-releasing factor (CRF) system in the central nucleus of the amygdala (CeA) may be a factor in genetically determined alcohol preference.


METHODS
To test this hypothesis, basal and restraint stress-induced CRF efflux in the CeA was determined by microdialysis in Sardinian alcohol-preferring (sP) and nonpreferring (sNP) rats. In addition, differences in anxiety-like behavior between sP and sNP rats were evaluated by using the elevated plus maze and conditioned defensive burying tests.


RESULTS
Basal dialysate CRF levels in the CeA were elevated in the alcohol-preferring line (sP, 281.2+/-83.96 pg/ml; sNP, 70.2+/-16.76 pg/ml; p < 0.05). In contrast, no differences in whole-tissue CRF content in the CeA were observed (sP, 1143+/-142 ng/mg protein; sNP, 1181+/-139 ng/mg protein). Restraint stress elevated CRF dialysate concentrations in both sP and sNP rats. Rats of the sP line exhibited more anxiety-like behavior than sNP rats in the elevated plus maze but not in the conditioned defensive burying test.


CONCLUSIONS
The results suggest that ethanol-preferring sP rats show a dysregulation in basal CRF release within the CeA that may, in turn, heighten ethanol intake and increase susceptibility to anxiogenic stimuli in these animals.
Richter
R M
RM
Department of Molecular Neurobiology, Institute of Molecular Pharmacology, Berlin, Germany. richter@fmp-berlin.de
Zorrilla
E P
EP
Basso
A M
AM
Koob
G F
GF
Weiss
F
F
D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D001143:Arousal / Q000235:genetics* / Q000502:physiology; D001931:Brain Mapping; D003214:Conditioning, Classical / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005838:Genotype; D008297:Male; D018782:Maze Learning / Q000502:physiology; D017551:Microdialysis; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D012641:Selection, Genetic; D013239:Stereotyped Behavior / Q000502:physiology
D003346:Corticotropin-Releasing Hormone