Effects of antidepressants on γ-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⁺ concentration ([Ca²⁺](i)) increases induced by γ-aminobutyric acid (GABA) or N-methyl-D-aspartate (NMDA) in primary cultured rat cortical neurons using fluorescence imaging. Acute treatment with imipramine inhibited GABA- and NMDA-induced increases in [Ca²⁺](i) in a concentration-dependent manner. Doses of 30 μM clomipramine, desipramine, amoxapine and maprotiline also inhibited both the GABA- and NMDA-induced [Ca²⁺](i) increases significantly. Both inhibitory effects of the five major antidepressants on the GABA- or the NMDA-induced [Ca²⁺](i) increases were well-correlated. Imipramine could 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 inhibitory effects are not related to specific receptors. One possibility is that these effects may be commonly mediated via part of the high-K⁺-induced [Ca²⁺](i) pathway. Copyright (C) 2000 S. Karger AG, Basel.