Activation of CB1 cannabinoid receptors in rat hippocampal slices inhibits potassium-evoked cholecystokinin release, a possible mechanism contributing to the spatial memory defects produced by cannabinoids.

Cannabinoid use is known to disrupt learning and memory in a number of species. cholecystokinin (CCK) release and CCK receptors have been implicated in spatial memory processes in rodents. Rat hippocampal CCK interneurons express cannabinoid 1 receptors (CB1). The CB1 agonist R(+)WIN 55,212-2 (WIN+), at 1 and 10 micromol, strongly inhibited potassium-evoked CCK release from rat hippocampal slices, while the inactive isomer S(-)WIN,55,212-3 (WIN-) had no effect. CCK release from cerebral cortical slices was not altered by WIN+.