Effects of Antidepressants on γ-Aminobutyric Acid- and N-Methyl-<i>D</i>-Aspartate-Induced Intracellular Ca²⁺ Concentration Increases in Primary Cultured Rat Cortical Neurons

Abstract

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.

Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms

“…Studies have reported that imipramine may also improve NMDA receptor regulation (Takebayashi et al, 2000). In fact, acute treatment with imipramine inhibits NMDA-induced increases in intracellular calcium ([Ca 2 þ ] i ) (Takebayashi et al, 2000).…”

Effect of the Antidepressant Desipramine on Cytosolic Ca²⁺ Movement and Proliferation in Human Osteosarcoma Cells

“…This study has explored the effect of desipramine on [ as inhibition of neurotransmitters-induced [Ca 2+ ] i increases in neurons [24] and blockade of voltage-dependent Ca 2+ channels in brain cortex synaptosomes [25]. Our data are the first to show that desipramine may increase [Ca 2+ ] i in osteoblasts.…”

Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells

“…It has been previously shown that acute treatment with maprotiline inhibits [Ca 2+ ] i increases induced in neurons by c-aminobutyric acid and N-methyl-D-aspartate (Takebayashi et al 2000). In contrast, chronic treatment with maprotiline amplifies serotonin-2A receptor-induced Ca 2+ mobilization in C6 glioma cells (Muraoka et al 1998); however, the possible effect of maprotiline on basal [Ca 2+ ] i is unclear.…”

“…At the cellular level, maprotiline was shown to modulate the electrophysiological properties of cardiac muscles (Igawa et al 1988), to inhibit c-aminobutyric acid-and N-methyl-D-aspartateinduced increases of intracellular Ca 2+ concentration ([Ca 2+ ] i ) in primary cultured rat cortical neurons (Takebayashi et al 2000), to amplify serotonin-2A (5-HT 2A ) receptor-induced Ca 2+ mobilization in C6 glioma cells (Muraoka et al 1998), to inhibit 22 Na + influx in bovine chromaffin cells (Arita et al 1987), and to block delayed rectifier potassium current in ventricular myocytes (Casis et al 2002).…”

“…Thus it is important to examine the effect of an agent on cellular Ca 2+ signaling in order to understand its in vitro effect. Although maprotiline has been shown to alter agonist-induced [Ca 2+ ] i rises (Takebayashi et al 2000;Muraoka et al 1998), the effect of maprotiline on basal [Ca 2+ ] i has not been carefully explored. This issue is important because an altered basal [Ca 2+ ] i may change agonist-induced [Ca 2+ ] i rise.…”