CHOLECYSTOKININ-8S INCREASES DYNORPHIN-B, ASPARTATE AND GLUTAMATE RELEASE IN THE FRONTOPARIETAL CORTEX OF THE RAT VIA DIFFERENT RECEPTOR SUBTYPES

The effect of sulphated cholecystokinin-8 (CCK-8S) on extracellular dy norphin B, aspartate, glutamate and GABA levels in the rat fronto-pari etal cortex was investigated with in vivo microdialysis. The peptide w as infused through the microdialysis probe trying to mimic local CCK-8 S release. Basal levels of dynorphin B were around 20 pM, aspartate 10 0 nM, glutamate 600 nM and GABA 30 nM. CCK-8S (10 mu M) induced a appr oximate to 3-fold increase in extracellular dynorphin B, aspartate and glutamate levels, while GABA levels were only slightly increased. The effect of CCK-8S was restricted to the stimulated neocortex. Systemic pretreatment with the CCKB antagonist, L-365, 260, but not with the C CKA antagonist, L-364, 718, significantly antagonised the effect of CC K-8S on cortical dynorphin B and aspartate release. However, both CCKA and CCKB antagonists inhibited the increase in cortical glutamate lev els. Thus, the present results indicate that cortical CCK release exer ts a stimulatory modulation on cortical dynorphin B and aspartate rele ase via the CCKB receptor subtype, and on glutamate release via both C CKA and CCKB receptor subtypes. Considering electrophysiological evide nce that CCK increases neuronal firing rates in many brain regions, it may be suggested that CCK represents a stimulatory system modulating the function of the neocortex.