Behavioral and cortical EEG evaluations confirm the roles of both CCKA and CCKB receptors in mouse CCK-induced anxiety

• Published in: Behavioural brain research 2013-01, Vol.237, p.325-332
• Main Authors: Li, Heng, Ohta, Hidenobu, Izumi, Hitomi, Matsuda, Yoshiki, Seki, Mika, Toda, Takako, Akiyama, Misaki, Matsushima, Yukiko, Goto, Yu-ichi, Kaga, Makiko, Inagaki, Masumi
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - drug effects; Analysis of Variance; Animals; Anxiety - chemically induced; Anxiety - pathology; Anxiety - physiopathology; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Brain CCKA and CCKB receptors; Brain Mapping; Brain Waves - drug effects; Brain Waves - physiology; c-Fos immunopositive neurons; CCK-4; Devazepide - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; EEG monitoring; Electroencephalography; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Indoles - pharmacology; Injections, Intraventricular; Male; Maze Learning - drug effects; Meglumine - analogs & derivatives; Meglumine - pharmacology; Mice; Mice, Inbred C57BL; Mouse anxiety tests; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptor, Cholecystokinin A - antagonists & inhibitors; Receptor, Cholecystokinin A - metabolism; Receptor, Cholecystokinin B - antagonists & inhibitors; Receptor, Cholecystokinin B - metabolism; Spectrum Analysis; Tetragastrin - toxicity
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2012.09.051

► The roles of CCKA and CCKB receptors in the brain on CCK-4-induced anxiety were examined using a mouse model. ► Not only CCKB receptors but also CCKA receptors in the brain play important roles in regulating anxiety-like behaviors in mice. ► Delta and theta frequency band monitoring in cortical EEG is as useful as behavioral tests for assessing the levels of anxiety. This study investigated the roles of cholecystokinin (CCK)A and CCKB 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 CCKA and CCKB receptors. The effects of CCKA and CCKB 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 (3μg/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 (0.5–5Hz frequency bands) and also in increase in c-Fos immunopositive neuron counts. These CCK-4 effects were completely suppressed by 1.0mg/kg CCKB receptor antagonist, CI-988, while the same amount of CCKA receptor antagonist, devazepide was partly able to suppress the same effects. These findings indicated that not only CCKB receptors but also CCKA 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.