ELECTROPHYSIOLOGICAL EVIDENCE FOR THE IMPLICATION OF CHOLECYSTOKININ IN THE MODULATION OF THE N-METHYL-D-ASPARTATE RESPONSE BY SIGMA-LIGANDS IN THE RAT CA(3) DORSAL HIPPOCAMPUS

Previous studies from our laboratory have demonstrated that low doses of selective sigma (sigma) ligands potentiate the response of pyramida l neurones to N-methyl-D-aspartate (NMDA) in the CA(3) region of the r at dorsal hippocampus. It has also been found that the neuropeptide ch olecystokinin (CCK) is involved in the effects induced by sigma ligand s on colonic motility. The present experiments were undertaken to dete rmine if this interaction is also present in the rat dorsal hippocampu s. Using microiontophoresis and in vivo extracellular recordings of ra t CA(3) dorsal hippocampus pyramidal neurones, we assessed the effects of CCKA and CCKB receptor antagonists on the potentiation of the NMDA response, induced by the intravenous administration of low doses of t he sigma ligands 1,3-di(2-tolyl)guanidine (DTG), (+)-pentazocine and J O-1784. The potentiation of the NMDA response induced by these sigma l igands was abolished by the selective CCKA receptor antagonist SR 2789 7, but not by the CCKB antagonist Cl-988. CCK-8S, applied with a low c urrent, insufficient to induce by itself an increase of the firing act ivity, markedly potentiated the response of NMDA without affecting sig nificantly that of quisqualate. SR 27897, but not Cl-988, significantl y reduced the potentiation of the NMDA response by CCK-8S. These resul ts suggest the existence of a functional interaction between CCK and s igma receptor-mediated effects in the dorsal hippocampus.