CCK_B-Receptor Activation Augments the Long-Term Potentiation in Guinea Pig Hippocampal Slices

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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 CCK_B receptor, non-sulfated CCK-8, dose-dependently augmented the magnitude of LTP. Concomitant application of a selective antagonist for the CCK_B 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 CCK_A-receptor antagonist, L-364, 718 (3S(−)-N-(2, 3-dihydro-1-methyl-2-oxo-5-phenyl-IH-1, 4-benzodiazepine)), had little effect. Thus, enhancement of LTP by CCK appears to be mediated by CCK_B 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.