Cholecystokinin-8S increases dynorphin B, aspartate and glutamate release in the fronto-parietal cortex of the rat via different receptor subtypes

Abstract

The effect of sulphated cholecystokinin-8 (CCK-8S) on extracellular dynorphin B, aspartate, glutamate and GABA levels in the rat fronto-parietal cortex was investigated with in vivo microdialysis. The peptide was infused through the microdialysis probe trying to mimic local CCK-8S release. Basal levels of dynorphin B were around 20 pM, aspartate 100 nM, glutamate 600 nM and GABA 30 nM. CCK-8S (10 microM) induced a approximately 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 CCKA antagonist, L-364, 718, significantly antagonised the effect of CCK-8S on cortical dynorphin B and aspartate release. However, both CCKA and CCKB antagonists inhibited the increase in cortical glutamate levels. Thus, the present results indicate that cortical CCK release exerts a stimulatory modulation on cortical dynorphin B and aspartate release via the CCKB receptor subtype, and on glutamate release via both CCKA and CCKB receptor subtypes. Considering electrophysiological evidence 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.

SR146131, a cholecystokinin-A receptor agonist, antagonizes prepulse inhibition deficits produced by dizocilpine and DOI

“…However, converging evidence has demonstrated CCK/glutamate interactions in rodent brain (You et al 1996(You et al , 1997. For example, CCK administration enhances glutamate release and this effect is blocked by CCK-A and CCK-B receptor antagonists (You et al 1997). Our data are consistent with a CCK-A receptor mediated mechanism contributing to the disruption of PPI by noncompetitive NMDA antagonists.…”

“…The distinct blockade of dizocilpineinduced disruption of PPI by SR146131 is therefore a surprising finding as well. However, converging evidence has demonstrated CCK/glutamate interactions in rodent brain (You et al 1996(You et al , 1997. For example, CCK administration enhances glutamate release and this effect is blocked by CCK-A and CCK-B receptor antagonists (You et al 1997).…”

Bidirectional modulation of GABAergic transmission by cholecystokinin in hippocampal dentate gyrus granule cells of juvenile rats

“…Cholecystokinin has been reported to increase GABA release in cerebral cortex (You et al 1997;Ferraro et al 1999;Siniscalchi et al 2003), neostriatum (You et al 1996), anterior nucleus accumbens (Lanza & Makovec, 2000) and hippocampus (Perez de la Mora et al 1993;Miller et al 1997). By contrast, CCK has also been reported not to change GABA release in the frontal-parietal cortex (Hickling et al 1997) and hippocampus (Migaud et al 1994;Breukel et al 1997).…”

Cannabinoid CB1 and Cholecystokinin CCK2 Receptors Modulate, in an Opposing Way, Electrically Evoked [3H]GABA Efflux from Rat Cerebral Cortex Cell Cultures: Possible Relevance for Cortical GABA Transmission and Anxiety

“…However, it cannot be excluded that the observed effects of the CB 1 and CCK 2 receptor activation were mediated, at least in part, by the respective inhibition and increase of glutamate release from cortical glutamate neurons (You et al, 1997;Domenici et al, 2006), which in turn could oppositely affect [ 3 H]GABA release from cortical cell culture preparation. That either CB 1 -or CCK receptorrelated drugs influenced the electrically evoked, but not spontaneous, [ 3 H]GABA efflux is not surprising, because this type of efflux is calcium-independent and tetrodotoxin-insensitive and may thus rather reflect a membrane transport process instead of a vesicular release (Tomasini and Antonelli, 1998).…”