Effects of cholecystokinin-receptor agonists on cortical 5-HT release in guinea pigs on the X-maze.
Exposure of guinea pigs to the elevated plus maze (X-maze), an animal model of anxiety, causes an increase of extracellular serotonin (5-HT) in the lateral prefrontal cortex monitored by microdialysis. The neuropeptide cholecystokinin (CCK) plays a role in the modulation of anxiety. To compare the roles of CCK receptors, the effects of the CCK-A receptor agonist A-71378, the CCK-A/B receptor agonist CCK-8S and the CCK-B receptor agonist BOC-CCK-4 on anxiety-related behavior and the 5-HT release in the prefrontal cortex were determined. None of the drugs changed the behavior of the guinea pigs and the cortical 5-HT release under resting conditions in the familiar home cage. A-71378 and CCK-8S had no effect on the behavior on exposure to the X-maze whereas BOC-CCK-4 induced an 'anxious' behavior. The results suggest that 'anxious' behavior induced by CCK is associated with selective CCK-B receptor stimulation. A-71378 inhibited the rise in 5-HT on exposure to the X-maze. CCK-8S had no effect and the anxiogenic BOC-CCK-4 potentiated the rise in 5-HT on the X-maze. Both CCK receptors mediate changes in 5-HT release under aversive conditions, but not in a resting state. The results suggest a receptor subtype-specific influence of CCK on behavior and 5-HT activity under aversive conditions.
Rex
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Institute of Pharmacology and Toxicology, Medical Faculty of the Humboldt University at Berlin, Germany.
Fink
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D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D002766:Cholecystokinin / Q000008:administration & dosage* / Q000737:chemistry / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D009842:Oligopeptides / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*
D009842:Oligopeptides; D011949:Receptors, Cholecystokinin; C063897:A 71378; D012701:Serotonin; D002766:Cholecystokinin