Effect of local cholecystokinin-8 administration on extracellular levels of amino acids and glycolytic products monitored by in vivo microdialysis in the fronto-parietal cortex of the rat.

The effects of local cholecystokinin-8 (CCK-8) administration on cortical extracellular levels of amino acids, catecholamines and metabolism products were studied in the halothane anaesthetized rat by in vivo microdialysis. CCK-8 (10 microM), administrated via a microdialysis probe, produced a significant increase in the levels of aspartate, glutamate and gamma-aminobutyric acid (GABA), but not of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), lactate and pyruvate, which were simultaneously monitored. The increase in aspartate and glutamate levels produced by CCK-8 was about 3-4-fold. The effect of CCK-8 on aspartate levels was significantly inhibited by the CCKB antagonist, L-365,260 (20 mg kg-1, s.c.), but not by the CCKA antagonist, L-364,718 (20 mg kg-1, s.c.). In contrast, the increase in glutamate levels was inhibited by both L-365,260 and L-364,718. GABA was slightly, but significantly increased (approximately 30%), by local CCK-8 and was inhibited by both CCK antagonists. The present results show that CCK-8 exerts a strong modulatory action on both aspartate and glutamate release in rat cortex. While the effect of CCK-8 on aspartate is selectively mediated via CCKB receptor subtype, the effect of CCK-8 on glutamate appears to be mediated via both CCKA and CCKB receptor subtypes.