Opposing effects of two CCK(B) agonists on the retrieval phase of a two-trial memory task after systemic injection in the rat.

The effects of two selective CCK(B) agonists, BC 264 and BC 197, on memory processes were investigated in rats using a recently developed two-trial recognition memory task. Control animals showed recognition memory after a 2 but not a 6 h time interval between the two trials, thus allowing a memory impairing (2 h) or improving (6 h) effect of pharmacological treatments to be measured. Drugs were injected i.p. before the second trial (retrieval phase). This experimental procedure was first studied with scopolamine and DL-amphetamine, for which a significant deficit after a 2 h interval or improvement after a 6 h interval of performance was observed, respectively. The CCK(B) agonist, BC 264, was ineffective after a 2 h time interval, whereas the dose of 0.3 microg/kg significantly enhanced performance after a 6 h inter-trial interval. In contrast, BC 197 (30 microg/kg) produced a significant disruption of performance after a 2 h inter-trial interval but was without effect after a 6 h time interval. The effects of the two CCK(B) agonists were abolished by pretreatment with a selective CCK(B) antagonist, L365,260 but not by a selective CCK(A) antagonist, L364,718. The present results suggest that CCK(B) receptors display functional heterogeneity and that CCK(B) agonists like BC 264 could offer a new perspective for the treatment of attentional and/or memory deficits.