Fluoxetine suppresses synaptically induced [Ca2+]i spikes and excitotoxicity in cultured rat hippocampal neurons

Kim, Hee Jung; Kim, Tae Hyeong; Choi, Se Joon; Hong, Yi Jae; Yang, Ji Seon; Sung, Ki-Wug; Rhie, Duck-Joo; Hahn, Sang June; Yoon, Shin Hee

doi:10.1016/j.brainres.2012.10.062

Cited by 23 publications

(25 citation statements)

References 68 publications

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“…However, fluoxetine has inhibitory effects on AMPA and NMDA receptors (Szasz et al, 2007; Kim et al, 2013) and therefore, decreased fEPSPs should be expected. In consequence, the most straightforward explanation is that larger spines are able to elicit larger post-synaptic responses.…”

Section: Discussionmentioning

confidence: 99%

Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield

Rubio¹,

Ampuero²,

Sandoval³

et al. 2013

Front. Cell. Neurosci.

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Antidepressant drugs are usually administered for several weeks for the treatment of major depressive disorder. However, they are also prescribed in several additional psychiatric conditions as well as during long-term maintenance treatments. Antidepressants induce adaptive changes in several forebrain structures which include modifications at glutamatergic synapses. We recently found that repetitive administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine to naïve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions. This was associated with an increase of GluA2-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA-Rs) in telencephalic postsynaptic densities. To unravel the functional significance of such a synaptic re-arrangement, we focused on glutamate neurotransmission in the hippocampus. We evaluated the effect of four weeks of 0.7 mg/kg fluoxetine on long-term potentiation (LTP) and long-term depression (LTD) in the CA1 hippocampal subfield. Recordings in hippocampal slices revealed profound deficits in LTP and LTD at Schaffer collateral-CA1 synapses associated to increased spine density and enhanced presence of mushroom-type spines, as revealed by Golgi staining. However, the same treatment had neither an effect on spine morphology, nor on LTP and LTD at perforant path-CA1 synapses. Cobalt staining and immunohistochemical experiments revealed decreased AMPA-R Ca2+ permeability in the stratum radiatum (s.r.) together with increased GluA2-containing Ca2+ impermeable AMPA-Rs. Therefore, 4 weeks of fluoxetine treatment promoted structural and functional adaptations in CA1 neurons in a pathway-specific manner that were selectively associated with impairment of activity-dependent plasticity at Schaffer collateral-CA1 synapses.

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Section: Discussionmentioning

confidence: 99%

Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield

Rubio¹,

Ampuero²,

Sandoval³

et al. 2013

Front. Cell. Neurosci.

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show abstract

“…Rat hippocampal neurons from embryonic day 17 were grown in primary culture as described previously (Kim et al, 2013). All procedures of animal research were provided in accordance with the Laboratory Animals Welfare Act, the Guide for the Care and Use of Laboratory Animals and the Guidelines and Policies for Rodent Experiment provided by the Institutional Animal Care and Use Committee (IACUC) in College of Medicine, The Catholic University of Korea (Approval number: CUMC-2014-0144-01).…”

Section: Culture Of Primary Rat Hippocampal Cellsmentioning

confidence: 99%

Cyanidin-3-glucoside inhibits glutamate-induced Zn2+ signaling and neuronal cell death in cultured rat hippocampal neurons by inhibiting Ca2+-induced mitochondrial depolarization and formation of reactive oxygen species

Yang

Perveen

et al. 2015

Brain Research

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“…Our data are in agreement with results of Kim et al . (), demonstrating direct inhibition of synaptically‐induced Ca 2+ I spikes and cell death in cultured hippocampal cells by FLX. Given the medical importance of FLX, finding a new target for this drug may be important for neuropharmacology.…”

Section: Discussionmentioning

confidence: 92%

“…However, Kim et al . () showed that FLX has an inhibitory effect on Ca 2+ ‐permeable AMPA receptors. The mechanism of this inhibitory action is unclear.…”

Section: Introductionmentioning

confidence: 99%

Non‐classical mechanism of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor channel block by fluoxetine

Barygin

Komarova

Tikhonova

et al. 2014

Eur J of Neuroscience

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Antidepressants have many targets in the central nervous system. A growing body of data demonstrates the influence of antidepressants on glutamatergic neurotransmission. In the present work, we studied the inhibition of native Ca(2+)-permeable and Ca(2+)-impermeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in rat brain neurons by fluoxetine. The Ca(2+)-impermeable AMPA receptors in CA1 hippocampal pyramidal neurons were weakly affected. The IC50 value for the inhibition of Ca(2+)-permeable AMPA receptors in giant striatal interneurons was 43 ± 7 μM. The inhibition of Ca(2+)-permeable AMPA receptors was voltage dependent, suggesting deep binding in the pore. However, the use dependence of fluoxetine action differed markedly from that of classical AMPA receptor open-channel blockers. Moreover, fluoxetine did not compete with other channel blockers. In contrast to fluoxetine, its membrane-impermeant quaternary analog demonstrated all of the features of channel inhibition typical for open-channel blockers. It is suggested that fluoxetine reaches the binding site through a hydrophobic access pathway. Such a mechanism of block is described for ligands of sodium and calcium channels, but was never found in AMPA receptors. Molecular modeling suggests binding of fluoxetine in the subunit interface; analogous binding was proposed for local anesthetics in closed sodium channels and for benzothiazepines in calcium channels.

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Fluoxetine suppresses synaptically induced [Ca2+]i spikes and excitotoxicity in cultured rat hippocampal neurons

Cited by 23 publications

References 68 publications

Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield

Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield

Cyanidin-3-glucoside inhibits glutamate-induced Zn2+ signaling and neuronal cell death in cultured rat hippocampal neurons by inhibiting Ca2+-induced mitochondrial depolarization and formation of reactive oxygen species

Non‐classical mechanism of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor channel block by fluoxetine

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