The effects of cholecystokinin and cholecystokinin antagonists on synaptic function in the CA1 region of the rat hippocampal slice.

The effects of two CCK antagonists, benzotript and proglumide, and of sulfated and non-sulfated cholecystokinin octapeptide (CCK-8-S and CCK-8-NS), were studied in the CA1 region of the rat hippocampal slice. Both benzotript and proglumide shifted presynaptic volley (prevolley) vs population spike input/output (I/O) curves for Schaffer collateral-commissural synaptic transmission to the right. This result indicates that the antagonists had a net depressant effect on synaptic transmission. CCK-8-S shifted prevolley vs population spike I/O curves to the left, indicating a net excitatory effect. Analysis of component I/O curves indicated that CCK-8-S and the CCK antagonists were acting postsynaptically by changing CA1 pyramidal cell threshold. CCK-8-NS had no significant effect on overall or component I/O functions. These findings suggest that endogenous CCK is released, directly or indirectly, upon stimulation of the Schaffer collateral-commissural fibers and increases the excitability of CA1 pyramidal cells.