caa a22 4500 469077786 CHVBK 20180323132940.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF00167567 doi (NATIONALLICENCE)springer-10.1007/BF00167567 Modulation by sigma ligands of N -methyl- D -aspartate-induced [3H]noradrenaline release in the rat hippocampus: G -protein dependency [Elektronische Daten] [François Monnet, Pierre Blier, Guy Debonnel, Claude de Montigny] Summary: The effects of the high affinity sigma (σ) ligands 1,3-di(2-tolyl)guanidine (DTG), (+)N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-ylamine 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 SpragueDawley 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 (σ) 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 (σ) 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. Both the in vivo PTX and the in vitro NEM pretreatments abolished the potentiating effects of JO-1784 and (+)3-PPP, and shifted the concentration-effect curve for DTG-induced suppression of NMDA-evoked release of [3H]NA to the right. These results suggest that the (σ) receptors mediating the effects of JO-1784, (+)3-PPP and DTG on NMDA-evoked release of [3H]NA are coupled to Gi/o proteins. Springer-Verlag, 1992 Noradrenaline release nationallicence Sigma binding sites nationallicence NMDA nationallicence Gi/o protein nationallicence Haloperidol nationallicence DTG nationallicence Monnet François Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada aut Blier Pierre Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada aut Debonnel Guy Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada aut de Montigny Claude Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/1(1992-07-01), 32-39 0028-1298 346:1<32 1992 346 210 https://doi.org/10.1007/BF00167567 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00167567 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Monnet François Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada aut NATIONALLICENCE 700 1- Blier Pierre Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada aut NATIONALLICENCE 700 1- Debonnel Guy Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada aut NATIONALLICENCE 700 1- de Montigny Claude Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, H3A 1A1, Montréal, Québec, Canada aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/1(1992-07-01), 32-39 0028-1298 346:1<32 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer