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Gandolfi O, Gaggi R, Voltattorni M, Dall'Olio R. 
“The activation of serotonin receptors prevents glutamate-induced neurotoxicity and NMDA-stimulated cGMP accumulation in primary cortical cell cultures”. 
Pharmacol Res. 2002 Nov 06;46(5):409-14.
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.
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