title: Blockade of CRF1 and CCK2 receptors attenuated the elevated anxiety-like behavior induced by immobilization stress.
abstract: Two highly co-localized neurotransmitters: corticotropin-releasing factor (CRF) and cholecystokinin (CCK), have been implicated in the development of stress-related anxiety disorders. This study was designed to examine the role of CRF1 and CCK2 receptors on the anxiety-like behavior induced by immobilization stress. Our results showed that 30-min immobilization enhanced the anxiety-like behavior in C57BL/6J mice examined in the elevated plus maze (EPM). The combined pretreatment of CR2945 (a CCK2 receptor antagonist) and antalarmin (a CRF1 receptor antagonist) fully blocked this elevated anxiety-like behavior, while the application of CR2945 or antalarmin alone showed only partial effects. The increased expression of CRF1 and CCK2 receptors at protein levels in three anxiety-related brain regions: cortex, hippocampus and hypothalamus, was detected by Western blot. The increased mRNA expression of CCK, CRF, CCK2 and CRF1 receptors was also examined by real-time RT-PCR. Our study demonstrated that the blockade of CRF1 and CCK2 receptors attenuated the elevated anxiety-like behavior induced by immobilization stress, suggestive of the CRF and CCK systems contributing to the development of stress-related anxiety behavior.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Jachim
authors.initials: J
authors.lastname: Spiess
authors.forename: Peter T-H
authors.initials: PT
authors.lastname: Wong
authors.forename: Yi Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D015153:Blotting, Western; D007103:Immobilization; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors* / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological; D000099052:CRF Receptor, Type 1
chemical_list: D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1