Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 361, Issue 1, pp 33–38

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

  • M. Lanza
  • F. Makovec
Original Article

DOI: 10.1007/s002109900161

Cite this article as:
Lanza, M. & Makovec, F. Naunyn-Schmiedeberg's Arch Pharmacol (2000) 361: 33. doi:10.1007/s002109900161


The effects of cholecystokinin sulfate octapeptide (CCK-8S) on [3H]γ-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 µM CCK-8S ranged from 37% to 42%. CR 2945, (β-[2-[[2-(8-azaspiro[4.5]dec-8-ylcarbonyl)-4,6-dimethylphenyl]-amino]-2-oxoethyl]-(R)-1-naphthalenepropanoic acid), a potent and selective nonpeptidergic CCKB antagonist, concentration-dependently blocked CCK-8S effect (IC50=2.16 nM). CCK-8S-induced increase in [3H]GABA overflow was completely blocked by 1 µM tetrodotoxin. Both the α-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 GABAA receptor antagonist, was completely ineffective. Phaclofen, a selective GABAB 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 CCKB receptors modulating [3H]GABA release from anterior accumbal punches may not be present on GABAergic terminals but could be located on glutamatergic interneurons.

Cholecystokinin γ-Aminobutyric acid release Anterior nucleus accumbens CR 2945 Cholecystokinin B receptors α-Amino-3-hydroxy-5-methylisoxazole-4-propionate receptors

Copyright information

© Springer-Verlag 0000

Authors and Affiliations

  • M. Lanza
    • 1
  • F. Makovec
    • 1
  1. 1.Rotta Research Laboratorium S.p.A., Via Valosa di Sopra 7/9, I-20052 Monza, Italy