title: Behavioral and cortical EEG evaluations confirm the roles of both CCKA and CCKB receptors in mouse CCK-induced anxiety.
abstract: This study investigated the roles of cholecystokinin (CCK)(A) and CCK(B) receptors on CCK-4-induced anxiety-like behaviors in mice through behavioral and neural evaluations. Anxiety-like behaviors in mice were induced by an intracerebroventricular (i.c.v.) administration of CCK-4, which can bind to both CCK(A) and CCK(B) receptors. The effects of CCK(A) and CCK(B) receptor antagonists (devazepide and CI-988, respectively) were examined using mouse anxiety tests (elevated-plus maze and light-dark box) and also by examining neuronal activities through EEG monitoring and c-Fos immunohistochemistry in the cortex and amygdala. CCK-4 (3 μg/kg of body weight i.c.v.) significantly induced mouse anxiety-like behaviors in the anxiety tests and also affected their EEG patterns with respect to pre-drug tracing, resulting in increase in spectral power in relative power distribution in the delta and theta bands (0.5-5 Hz frequency bands) and also in increase in c-Fos immunopositive neuron counts. These CCK-4 effects were completely suppressed by 1.0mg/kg CCK(B) receptor antagonist, CI-988, while the same amount of CCK(A) receptor antagonist, devazepide was partly able to suppress the same effects. These findings indicated that not only CCK(B) receptors but also CCK(A) receptors in the brain play important roles in regulating anxiety-like behaviors in mice. The present study also proposed a possibility that cortical EEG is useful for assessing anxiety.
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawa Higashi, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Ohta
authors.forename: Hitomi
authors.initials: H
authors.lastname: Izumi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Mika
authors.initials: M
authors.lastname: Seki
authors.forename: Takako
authors.initials: T
authors.lastname: Toda
authors.forename: Misaki
authors.initials: M
authors.lastname: Akiyama
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Makiko
authors.initials: M
authors.lastname: Kaga
authors.forename: Masumi
authors.initials: M
authors.lastname: Inagaki
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001931:Brain Mapping; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D020109:Devazepide / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005786:Gene Expression Regulation / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013057:Spectrum Analysis; D013758:Tetragastrin / Q000633:toxicity*
chemical_list: D007211:Indoles; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D013758:Tetragastrin; C065599:PD 134308; D008536:Meglumine; D020109:Devazepide