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.