The Effects of Cholecystokinin A and B Receptor Antagonists on Exploratory Behaviour in the Elevated zero-maze in Rat

Abstract

The aim of the present study was to investigate the effects of cholecystokinin (CCK) CCK A and CCK B receptor antagonists SR 27897 B, devazepide, L 365260 and PD 135158 (CAM 1028) on exploratory behaviour in the elevated zero-maze in the rat. For further validation of the elevated zero-maze, the effects of a reference anxiolytic diazepam (0.25, 0.5, 1.0, 2.0 mg/kg), a non-benzodiazepine (BDZ) anxiolytic buspirone (0.04, 0.2, 1.0, 5.0 mg/kg), BDZ receptor inverse agonists FG 7142 (5, 10, 15,20 mg/kg) and DMCM (0.1, 0.5, 1.0, 1.5 mg/kg), and a BDZ receptor antagonist flumazenil (10 mg/kg) were studied. Diazepam decreased the number of stretched-attend postures in all doses used and increased the percentage of time spent exploring in open parts at doses of 0.5 and 1.0 mg/kg. The effects of diazepam were blocked by flumazenil. FG 7142 and DMCM had effects only in subconvulsive doses (20 mg/kg and 1.5 mg/kg). Flumazenil and buspirone failed to show any effect. The CCK A receptor antagonists were also without any effect. The CCK B receptor antagonists L 365260 (1.0 and 5.0 mg/kg) and PD 135158 (100 μg/kg) had a significant anxiolytic-like effect. The CCK B receptor antagonists increased the number of open part entries, the number of head dips, the percentage of time spent exploring in the open part and decreased the number of stretched-attend postures. These data support the hypothesis of the involvement of the CCK B receptor subtype in the neurobiological mechanisms of anxiety. © 1997 Elsevier Science Ltd. All rights reserved.