CCKB-receptor activation augments the long-term potentiation in guinea pig hippocampal slices

Effects of cholecystokinin octapeptide (CCK-8) on long-term potentiation (LTP) of CA1 synaptic transmission induced by tetanic stimulation of the input fibers were examined in guinea pig hippocampal slices. CCK-8 and a selective agonist for the CCKB receptor, non-sulfated CCK-8, dose-dependently augmented the magnitude of LTP. Concomitant application of a selective antagonist for the CCKB-receptor subtype, L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepine-3-yl)-N'-(3-methylphenyl)urea), completely blocked the augmentation of LTP induced by CCK-8, whereas a selective CCKA-receptor antagonist, L-364,718 (3S(-)-N-(2,3-dihydro-1-methyl-2- oxo-5-phenyl-1H-1,4-benzodiazepine)), had little effect. Thus, enhancement of LTP by CCK appears to be mediated by CCKB receptors. Furthermore, CCK-8 enhanced paired-pulse facilitation at a concentration of 10(-7) M without affecting the amplitude of the population spike induced by single stimulation. This effect was mimicked by a low dose of tetraethylammonium (TEA), a K+ channel blocker. Moreover, both CCK-8 and TEA reduced the late component of evoked field potentials. This late evoked potential was diminished by increasing the extracellular K+ concentration. It is suggested that CCK-8 reduces the K+ conductance in CA1 pyramidal neurons. This reduction in the K+ conductance might be related to enhancement of the LTP.