title: The activation of serotonin receptors prevents glutamate-induced neurotoxicity and NMDA-stimulated cGMP accumulation in primary cortical cell cultures.
abstract: In the present study, we performed experiments on primary cell cultures from rat neocortex to assess the effects of the selective serotonergic 5HT(1A), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or 5HT(2), (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) agonists on neuronal death induced by 15min exposure to (-)glutamate (300 microM) as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The results show that both drugs attenuated (-)glutamate-induced neurotoxicity and this effect was fully antagonized by the selective antagonists of 5HT(1) (NAN-190) or 5HT(2) (ketanserin) receptors.The effects of the selective serotonergic agonists on the production of cyclic GMP (cGMP) accumulation induced by N-methyl-D-aspartate (NMDA) in the same neuronal preparation were also evaluated. Only the 5HT(2) agent, but not 8-OH-DPAT, per se, decreased basal cGMP levels. In contrast, both drugs attenuated the NMDA-induced cGMP accumulation in this cell preparation. The unexpected similar behavior of 5HT(1) and 5HT(2) agonists towards glutamate-induced neurotoxicity and NMDA-induced cGMP accumulation in primary cell cultures is discussed. It is concluded that primary cell cultures from rat cerebral cortex could represent a suitable experimental model to search novel neuroleptics which exert their effects via 5HT receptors.
authors.affiliation: Department of Pharmacology, University of Bologna, Via Irnerio 48, Italy. gandolfi@biocfarm.unibo.it
authors.forename: O
authors.initials: O
authors.lastname: Gandolfi
authors.forename: R
authors.initials: R
authors.lastname: Gaggi
authors.forename: M
authors.initials: M
authors.lastname: Voltattorni
authors.forename: R
authors.initials: R
authors.lastname: Dall'Olio
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D007215:Indophenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; D018698:Glutamic Acid; D007215:Indophenol; D016202:N-Methylaspartate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006152:Cyclic GMP