Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCK(B) receptors located on glutamatergic interneurons
Lanza, Makovec (2000) Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCK(B) receptors located on glutamatergic interneurons Naunyn Schmiedebergs Arch Pharmacol (IF: 3) 361(1) 33-8Abstract
The effects of cholecystokinin sulfate octapeptide (CCK-8S) on [3H]gamma-aminobutyric acid (GABA) release have been studied in the anterior side of the rat nucleus accumbens on tissue punches exposed in superfusion to 30 mM KCl. CCK-8S in a concentration dependent manner (10-3000 nM) increased K+-evoked [3H]GABA release (EC50=192 nM). The increase caused by 1 microM CCK-8S ranged from 37% to 42%. CR 2945, (beta-[2-[[2-(8-azaspiro[4.5]dec-8-ylcarbonyl)-4,6-dimethylp henyl]-amino]-2-oxoethyl]-(R)-1-naphthalenepropanoic acid), a potent and selective nonpeptidergic CCK(B) antagonist, concentration-dependently blocked CCK-8S effect (IC50=2.16 nM). CCK-8S-induced increase in [3H]GABA overflow was completely blocked by 1 microM tetrodotoxin. Both the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) and the N-methyl-D-aspartic acid (NMDA) receptor antagonist dizocilpine (MK-801) antagonized the CCK-8S effect. By contrast, (+)-bicuculline, a GABA(A) receptor antagonist, was completely ineffective. Phaclofen, a selective GABA(B) antagonist, increased K+-evoked [3H]GABA release but did not affect the facilitative effect of CCK-8S. Moreover, tetrodotoxin failed to block AMPA-evoked [3H]GABA release but completely prevented the effect of NMDA (Mg2+ free conditions). The data presented suggest that CCK(B) receptors modulating [3H]GABA release from anterior accumbal punches may not be present on GABAergic terminals but could be located on glutamatergic interneurons.
Links
http://www.ncbi.nlm.nih.gov/pubmed/10651144http://dx.doi.org/10.1007/s002109900161
