Ethological analysis of cholecystokinin (CCKA and CCKB) receptor ligands in the elevated plus-maze test of anxiety in mice

The literature on the effects of CCK receptor manipulations in animal models of anxiety is rife with inconsistency, and the data subject to a variety of methodological and interpretative difficulties. In the present paper, the effects of a range of CCK receptor ligands on anxiety in male mice have been assessed using an ethological version of the elevated plus-maze test. Compounds selected for study were the agonists, CCK-4 and CCK-8s (12.5-100 mu g/kg), and the antagonists, devazepide, L-365,260 and PD 135158 (1.0 mu g/kg-1.0 mg/kg). CCK-4 failed to produce any significant behavioural effects over the dose range tested, while treatment with the sulphated octapeptide, CCK-8s, induced signs of behavioural inhibition at 100 mu g/kg without altering anxiety-related indices. Furthermore, in contrast to the clear anxiolytic profile of diazepam (1 mg/kg), and despite the comprehensive behavioural profiles yielded by ethological analysis, all three CCK receptor antagonists studied (devazepide, L-365, 260 and PD 135158) were found to be without significant effect under present test conditions. Together, present findings provide little support for the involvement of CCK receptor mechanisms in anxiety and, in particular, the form of anxiety evoked in mice by exposure to a plus-maze.