CCKB receptors mediate CCK-8S-induced activation of dorsal hippocampus CA3 pyramidal neurons: an in vivo electrophysiological study in the rat.

The sulphated octapeptide C-terminal fragment of cholecystokinin (CCK-8S) is present in high concentration in the mammalian brain, where it acts via two types of receptor denoted CCKA and CCKB. In the dorsal hippocampus, CCK-8S exerts a potent excitatory effect on pyramidal neurons. The present electrophysiological study was undertaken to determine which CCK receptor type mediates this neuronal activation. Using in vivo extracellular unitary recordings of CA3 pyramidal hippocampal neurons, we compared the effect of SNF-8702, a potent selective CCKB receptor agonist, to that of CCK-8S, and assessed the effects of selective CCKA and CCKB antagonists. CCK-8S and SNF-8702, microiontophoretically applied on the same neurons produced a similar degree and pattern of activation. Both CCK-8S- and SNF-8702-induced activations were suppressed by the microiontophoretic application of the CCKB antagonist CI-988, but not by that of the CCKA antagonist SR 27897. CCK-8S-induced activation was not significantly modified by the intravenous administration of the CCKA antagonists devazepide and SR 27897. However, it was reduced by the CCKB antagonist PD 135158, administered intravenously or intracerebroventricularly, and by the intravenous administration of the CCKB antagonist L-365,260. The intravenous administration of PD 135158 also reduced SNF-8702-induced activations. These results indicate that CCKB receptors mediate CCK-8S-induced activation of rat CA3 pyramidal neurons.