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 15 min exposure to (−)glutamate (300 μM) 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.