The release of [3H]gamma-aminobutyric acid ([3H]GABA) from rat striatal slices before and during electrical field stimulation (EFS) was measured. Electrical stimulation (10 Hz) induced an increase of Ca(++)- and tetrodotoxin-sensitive [3H]GABA release from the striatal slices. In the presence of sulphated octapeptide of cholecystokinin, CCK-8S (10(-9) M, 10(-8) M and 10(-7) M) both the basal and the electrically (10 Hz)-evoked release of [3H]GABA were dose-dependently increased. These effects of CCK-8S were abolished by tetrodotoxin (10(-6) M) and were not influenced by the CCK-A receptor antagonist loxiglumide (CR1505) (10(-7) M and 10(-6) M). The stimulant effect of CCK-8S was antagonized by the newly synthesized CCK-B selective receptor antagonist PD134308 (10(-7) M and 10(-6) M). These findings suggest that CCK-8 plays a neuromodulatory role in the regulation of GABAergic neuronal activity in the striatum. The activation of CCK-B receptors located on GABAergic neurons is involved in the GABA release-potentiating effect of CCK-8S in rat striatum.
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