Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCKB receptors located on glutamatergic interneurons

The effects of cholecystokinin sulfate octapeptide (CCK-8S) on [H-3]gamma-a minobutyric acid (GABA) release have been studied in the anterior side of t he 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+-e voked [H-3]GABA release (EC50=192 nM). The increase caused by 1 mu M CCK-8S ranged from 37% to 42%. CR 2945, (beta-[2-[[2-(8-azaspiro [4.5]dec-8-ylcar bonyl)-4,6-dimethylphenyl]-amino]-2-oxoethyl]-(R)-1-naphthalenepropanoic ac id), a potent and selective nonpeptidergic CCKB antagonist, concentration-d ependently blocked CCK-8S effect (IC50= 2.16 nM). CCK-8S-induced increase i n [H-3]GABA overflow was completely blocked by 1 mu M tetrodotoxin. Both th e alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA)/kainate rece ptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) and the N-methyl-D- aspartic acid (NMDA) receptor antagonist dizocilpine (MK-801) antagonized t he CCK-8S effect. By contrast, (+)-bicuculline, a GABA(A) receptor antagoni st, was completely ineffective. Phaclofen, a selective GABA(B) antagonist, increased K+-evoked [H-3]GABA release but did not affect the facilitative e ffect of CCK-8S. Moreover, tetrodotoxin failed to block AMPA-evoked [H-3]GA BA release but completely prevented the effect of NMDA (Mg2+ free condition s). The data presented suggest that CCKB receptors modulating [H-3]GABA release from anterior accumbal punches may not be present on GABAergic terminals b ut could be located on glutamatergic interneurons.