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 pr esent paper, the effects of a range of CCK receptor ligands on anxiety in male mice have been assessed using an ethological version of the e levated 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 pro duce any significant behavioural effects over the dose range tested, w hile treatment with the sulphated octapeptide, CCK-8s, induced signs o f behavioural inhibition at 100 mu g/kg without altering anxiety-relat ed indices. Furthermore, in contrast to the clear anxiolytic profile o f diazepam (1 mg/kg), and despite the comprehensive behavioural profil es yielded by ethological analysis, all three CCK receptor antagonists studied (devazepide, L-365, 260 and PD 135158) were found to be witho ut significant effect under present test conditions. Together, present findings provide little support for the involvement of CCK receptor m echanisms in anxiety and, in particular, the form of anxiety evoked in mice by exposure to a plus-maze.