title: Modulation by sigma ligands of N-methyl-D-aspartate-induced [3H]noradrenaline release in the rat hippocampus: G-protein dependency.
abstract: The effects of the high affinity sigma (sigma) ligands 1,3-di(2-tolyl)guanidine (DTG), (+)N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1- ethyl-but-3-en-1-yl-amine hydrochloride (JO-1784), (+)3-[3-hydroxyphenyl]-N-(1-propyl)piperidine hydrochloride [(+)3-PPP] and haloperidol were studied on N-methyl-D-aspartate (NMDA)-evoked release of [3H]noradrenaline (NA) from preloaded hippocampal slices made from Sprague-Dawley rats. The [3H]NA release was evoked once by a 4 min exposure to NMDA, 40 min after the beginning of superfusion with a Mg+(+)-free Krebs' solution. In the absence of any drug, NMDA evoked a concentration-dependent [3H]NA release. Mg++ and EGTA abolished the [3H]NA release induced by NMDA. JO-1784 and (+)3-PPP potentiated in a concentration-dependent manner NMDA-induced [3H]NA release, without affecting the basal outflow. DTG concentration-dependently inhibited the overflow of [3H]NA evoked by NMDA, without affecting the basal efflux. Haloperidol, which did not modify NMDA-evoked [3H]NA release by itself, completely prevented the effects of JO-1784, (+)3-PPP and DTG. In contrast, spiperone, also a potent dopamine receptor antagonist but with low affinity for sigma binding sites, failed to prevent the potentiation of NMDA-evoked release of [3H]NA by JO-1784 and (+)3-PPP. The possible involvement of Gi/o proteins in the modulation by sigma ligands of NMDA-evoked [3H]NA release in the rat hippocampus was also investigated. To this end, Gi/o proteins were inactivated with pertussis toxin (PTX), injected locally 3 to 11 days prior to the experiment or with in vitro preincubation with N-ethylmaleimide (NEM) for 30 min prior the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Psychiatry, McGill University, Montréal, Québec, Canada.
authors.forename: F P
authors.initials: FP
authors.lastname: Monnet
authors.forename: P
authors.initials: P
authors.lastname: Blier
authors.forename: G
authors.initials: G
authors.lastname: Debonnel
authors.forename: C
authors.initials: C
authors.lastname: de Montigny
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006146:Guanidines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D037342:Pertussis Toxin; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000494:pharmacology; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D002934:Cinnamates; D003521:Cyclopropanes; D006146:Guanidines; D010880:Piperidines; D010566:Virulence Factors, Bordetella; D014316:Tritium; D013134:Spiperone; D016202:N-Methylaspartate; C026539:preclamol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D008274:Magnesium; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D005033:Ethylmaleimide; D002118:Calcium; D009638:Norepinephrine; C065310:igmesine