Opposing effects of two CCKB agonists on the retrieval phase of a two-trial memory task after systemic injection in the rat

The effects of two selective CCKB agonists, BC 264 and BC 197, on memory pr ocesses were investigated in rats using a recently developed two-trial reco gnition memory task. Control animals showed recognition memory after a 2 bu t not a 6 h time interval between the two trials, thus allowing a memory im pairing (2 h) or improving (6 h) effect of pharmacological treatments to be measured. Drugs were injected i.p. before the second trial (retrieval phas e). This experimental procedure was first studied with scopolamine and DL-a mphetamine, for which a significant deficit after a 2 h interval or improve ment after a 6 h interval of performance was observed, respectively. The CC KB agonist, BC 264, was ineffective after a 2 h time interval, whereas the dose of 0.3 mu g/kg significantly enhanced performance after a 6 h inter-tr ial interval. In contrast, BC 197 (30 mu g/kg) produced a significant disru ption of performance after a 2 h inter-trial interval but was without effec t after a 6 h time interval. The effects of the two CCKB agonists were abol ished by pretreatment with a selective CCKB antagonist, L365,260 but not by a selective CCKA antagonist, L364,718. The present results suggest that CC KB receptors display functional heterogeneity and that CCKB agonists like B C 264 could offer a new perspective for the treatment of attentional and/or memory deficits. (C) 1999 Elsevier Science Ltd. All rights reserved.