sincalide and rimorphin

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.

Topics: Animals; Aspartic Acid; Benzodiazepinones; Devazepide; Dynorphins; Endorphins; Frontal Lobe; gamma-Aminobutyric Acid; Glutamic Acid; Hormone Antagonists; Male; Microdialysis; Neurons; Nootropic Agents; Parietal Lobe; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Sincalide

Sulphated cholecystokinin-8 (CCK-8) given into the neostriatum of the rat by in vivo microdialysis produced a concentration-dependent (1-100 microM) increase in extracellular aspartate (Asp) and dynorphin B (Dyn B), but not in glutamate, GABA or dopamine levels. The increase in Asp levels produced by 10 microM CCK-8 was approximately 10 fold and was inhibited (approximately 50%) by the CCKB antagonist L-365,260 (20 mg kg-1, i.p.), while the increase in Dyn B (approximately 2 fold) was totally abolished. Both increases were inhibited (approximately 50%) by local infusion of 10 microM of tetrodotoxin (TTX). Thus, CCK exerts modulatory effects in the basal ganglia, possibly by interacting with local neostriatal neurones releasing Asp, and with Dyn B-containing neurones projecting to the pars reticulata of the substantia nigra.

Topics: Animals; Aspartic Acid; Benzodiazepinones; Corpus Striatum; Dynorphins; Endorphins; Male; Microdialysis; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Sincalide; Tetrodotoxin