Cholecystokinin-8 increases K(+)-evoked [3H] gamma-aminobutyric acid release in slices from various brain areas.

[3H] gamma-Aminobutyric acid (GABA) release was studied in rat brain slices in the absence or presence of cholecystokinin-8 (CCK-8). [3H]GABA release under the conditions used was Ca(2+)-dependent and insensitive to the presence of the glial uptake blocker beta-alanine. While the basal release of [3H]GABA was not affected by CCK-8, the K(+)-stimulated release of [3H]GABA was significantly enhanced by 300 nM of CCK-8 in the caudate putamen, the substantia nigra, the hippocampal formation and the parietofrontal cortex. In the cerebral cortex the CCK-8 enhancement of [3H]GABA release was concentration-dependent and abolished by the CCKB receptor antagonists PD135,158 (1.0 nM) and L-365,260 (100 nM). A significant counteraction of the CCK-8 action was also found with the CCKA receptor antagonist L-364,718 (100 nM) but only in concentrations at which both CCKA and CCKB receptors are blocked. No CCK-8 effects on [3H]GABA release were observed when tetrodotoxin was superfused 5 min before the K(+)-induced [3H]GABA release. It is suggested that the enhancing actions of CCK-8 on K(+)-stimulated [3H]GABA release is mainly related to an activation of CCKB receptors.