Neuronal activity regulated pentraxin (narp) and GluA4 subunit of AMPA receptor may be targets for fluoxetine modulation

Heinrich, Isabella A.; Freitas, Andiara E.; Wolin, Ingrid A.V.; Nascimento, Ana Paula Machado; Walz, Roger; Rodrigues, Ana Lúcia S.; Leal, Rodrigo Bainy

doi:10.1007/s11011-021-00675-x

Cited by 8 publications

(3 citation statements)

References 89 publications

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“…Interestingly, the lowest concentration of fluoxetine tested here (10 µM), which is very likely reached during the treatment of depressive patients, affected the sIPSCs. Moreover, the antidepressant effects of both substances could be attributable to their interaction with different targets: serotonin transporters [80], nicotinic receptors [39][40][41], potassium channels [63], Ca 2+ -permeable AMPA receptors and/or T-type calcium channels [37,38,42,43], and GABA A receptors ( [34], this work), among others.…”

Section: Discussionmentioning

confidence: 85%

“…Assuming that both fluoxetine and norfluoxetine modulate different targets in addition to serotonin transport, another feasible way to explain the decrease in the frequency of sIPSCs in hippocampal stratum radiatum interneurons may be through their interaction with nicotinic acetylcholine receptors, Ca 2+ -permeable AMPA receptors, and/or T-type calcium channels [37,38,42,43]. It is known that both fluoxetine and norfluoxetine inhibit nicotinic acetylcholine receptors in a non-competitive manner [39][40][41]; in this context, interneurons of the hippocampal CA1 stratum radiatum selectively express the α7 nicotinic receptor, which is highly permeable to Ca 2+ [61,62].…”

Section: Discussionmentioning

confidence: 99%

“…It is also known that both fluoxetine and norfluoxetine inhibit the functioning and decrease the expression of a variety of receptors and channels related to Ca 2+ permeability. In this context, fluoxetine inhibits N-methyl-D-aspartate (NMDA) and Ca 2+ -permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) glutamate receptors in the neurons of the hippocampal CA1 area [37] and decreases the expression of the GluA4 AMPA receptor subunit in the GABAergic parvalbumin-positive interneurons of the prefrontal cortex [38]. Furthermore, fluoxetine and norfluoxetine inhibit, in a non-competitive manner, nicotinic acetylcholine receptors, including α7 nicotinic receptors, which are highly permeable to Ca 2+ [39][40][41].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Hippocampal GABAergic Transmission by Fluoxetine and Its Metabolite Norfluoxetine

Vázquez-Gómez,

Hernández-Abrego,

Mejía-Piedras

et al. 2024

Receptors

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Major depression is related to dysfunction of the GABAergic pathway. Interestingly, the antidepressant fluoxetine modifies GABAergic neurotransmission in human and animal models of depression. However, the effects of norfluoxetine (the main metabolite of fluoxetine) on GABAergic neurotransmission have not yet been studied. Therefore, we explored whether fluoxetine and/or norfluoxetine may regulate GABAergic transmission and whether these substances interact with GABAA receptors in hippocampal CA1 stratum radiatum interneurons. For these purposes, we recorded the firing profile, GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs), and currents induced by GABA puffs in stratum radiatum interneurons using both whole-cell current- and voltage-clamp techniques. Interneurons were selected according with their high firing profile. We found that both fluoxetine and norfluoxetine (at 20 µM) significantly decreased the frequency of sIPSCs without modifying their amplitude and decreased the amplitude of GABA-induced currents. These results indicate that fluoxetine and norfluoxetine decrease GABA release from neurons contacting stratum radiatum interneurons and negatively modulate GABAA receptors in these interneurons, resulting in their disinhibition, which in turn may contribute to increasing the inhibition of hippocampal CA1 pyramidal neurons.

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