Electrophysiological evidence for the implication of cholecystokinin in the modulation of the N-methyl-D-aspartate response by sigma ligands in the rat CA3 dorsal hippocampus.
Previous studies from our laboratory have demonstrated that low doses of selective sigma (sigma) ligands potentiate the response of pyramidal neurones to N-methyl-D-aspartate (NMDA) in the CA3 region of the rat dorsal hippocampus. It has also been found that the neuropeptide cholecystokinin (CCK) is involved in the effects induced by sigma ligands on colonic motility. The present experiments were undertaken to determine if this interaction is also present in the rat dorsal hippocampus. Using microiontophoresis and in vivo extracellular recordings of rat CA3 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 the sigma ligands 1,3-di(2-tolyl)guanidine (DTG), (+)-pentazocine and JO-1784. The potentiation of the NMDA response induced by these sigma ligands was abolished by the selective CCKA receptor antagonist SR 27897, but not by the CCKB antagonist Cl-988. CCK-8S, applied with a low current, insufficient to induce by itself an increase of the firing activity, markedly potentiated the response of NMDA without affecting significantly that of quisqualate. SR 27897, but not Cl-988, significantly reduced the potentiation of the NMDA response by CCK-8S. These results suggest the existence of a functional interaction between CCK and sigma receptor-mediated effects in the dorsal hippocampus.
Gronier
B
B
Department of Psychiatry, McGill University, Montreal, Québec, Canada.
Debonnel
G
G
D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002934:Cinnamates / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D004357:Drug Synergism; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology*; D007210:Indoleacetic Acids / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010423:Pentazocine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D002934:Cinnamates; D003521:Cyclopropanes; D006727:Hormone Antagonists; D007210:Indoleacetic Acids; D017480:Receptors, sigma; D013844:Thiazoles; C080460:SR 27897; D016202:N-Methylaspartate; D002766:Cholecystokinin; D012844:Sincalide; D010423:Pentazocine; C065310:igmesine