A role for glucocorticoid-signaling in depression-like behavior of gastrin-releasing peptide receptor knock-out mice.
Abstract Background. The gastrin-releasing peptide receptor (GRPR) is highly expressed in the limbic system, where it importantly regulates emotional functions and in the suprachiasmatic nucleus, where it is central for the photic resetting of the circadian clock. Mice lacking GRPR presented with deficient light-induced phase shift in activity as well altered emotional learning and amygdala function. The effect of GRPR deletion on depression-like behavior and its molecular signature in the amygdala, however, has not yet been evaluated. Methods. GRPR knock-out mice (GRPR-KO) were tested in the forced-swim test and the sucrose preference test for depression-like behavior. Gene expression in the basolateral nucleus of the amygdala was evaluated by micorarray analysis subsequent to laser-capture microdissection-assisted extraction of mRNA. The expression of selected genes was confirmed by RT-PCR. Results. GRPR-KO mice were found to present with increased depression-like behavior. Microarray analysis revealed down-regulation of several glucocorticoid-responsive genes in the basolateral amygdala. Acute administration of dexamethasone reversed the behavioral phenotype and alterations in gene expression. Discussion. We propose that deletion of GRPR leads to the induction of depression-like behavior which is paralleled by dysregulation of amygdala gene expression, potentially resulting from deficient light-induced corticosterone release in GRPR-KO.
Department of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna , Austria.
Francisco J
FJ
Monje
Eun-Jung
EJ
Kim
Maureen
M
Cabatic
Gert
G
Lubec
Kurt R
KR
Herkner
Daniela D
DD
Pollak
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000378:metabolism; D003863:Depression / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000378:metabolism; D018004:Receptors, Bombesin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005938:Glucocorticoids; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D003907:Dexamethasone; D003345:Corticosterone