Effects of antidepressants on gamma-aminobutyric acid- and N-methyl-D-aspartate-induced intracellular Ca2+ concentration increases in primary cultured rat cortical neurons

We investigated the effects of antidepressants on the intracellular Ca2+ co ncentration ([Ca2+](i)) increases induced by gamma-aminobutyric acid (GABA) or N-methyl-D-aspartate (NMDA) in primary cultured rat cortical neurons us ing fluorescence imaging, Acute treatment with imipramine inhibited GABA- a nd NMDA-induced increases in [Ca2+](i) in a concentration-dependent manner. Doses of 30 mu M clomipramine, desipramine, amoxapine and maprotiline also inhibited both the GABA- and NMDA-induced [Ca2+](i) increases significantl y, Both inhibitory effects of the five major antidepressants on the GABA- o r the NMDA-induced [Ca2+](i) increases were well-correlated, Imipramine cou ld inhibit significantly high-K+-induced [Ca2+](i) increases, Our previous study has already shown that the GABA-induced [Ca2+](i) increase involves a similar pathway to high-K+-induced Ca2+ influx, In conclusion, imipramine and several other antidepressants have acute inhibitory effects on the GABA -, NMDA- and high-K+-induced [Ca2+](i) increases, suggesting that these inh ibitory effects are not related to specific receptors, One possibility is t hat these effects may be commonly mediated via part of the high-K+-induced [Ca2+](i) pathway, Copyright (C) 2000 S. Karger AG,Basel.