ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
The SSRI citalopram affects fetal thalamic axon responsiveness to netrin-1 in vitro independently of SERT antagonism.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Advancing depression treatment: the role of sigma receptor ligands.Frontiers in neuroscience · 2025Review
- Chaperone Sigma1R and Antidepressant Effect.International journal of molecular sciences · 2020Review
- Article
- Two novel, putative mechanisms of action for citalopram-induced platelet inhibition.Scientific reports · 2018Article
- Efficacy and tolerability of pharmacotherapy for post-stroke depression: a network meta-analysis.Oncotarget · 2018Article
- Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport.Scientific reports · 2018Article
- Serotonin augmentation therapy by escitalopram has minimal effects on amyloid-β levels in early-stage Alzheimer's-like disease in mice.Alzheimer's research & therapy · 2017Article
- Blockade of the 5-HT transporter contributes to the behavioural, neuronal and molecular effects of cocaine.British journal of pharmacology · 2017Article
- Effect of Maternal ±Citalopram Exposure on P11 Expression and Neurogenesis in the Mouse Fetal Brain.ACS chemical neuroscience · 2017Article
- Circulating Plasma Micro RNAs in Patients with Major Depressive Disorder Treated with Antidepressants: A Pilot Study.Psychiatry investigation · 2016Article
- Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy.ACS chemical neuroscience · 2016Article
- Early-life serotonin dysregulation affects the migration and positioning of cortical interneuron subtypes.Translational psychiatry · 2015Article
- Placental serotonin: implications for the developmental effects of SSRIs and maternal depression.Frontiers in cellular neuroscience · 2013Article
- Serotonin homeostasis and serotonin receptors as actors of cortical construction: special attention to the 5-HT3A and 5-HT6 receptor subtypes.Frontiers in cellular neuroscience · 2013Article
- High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV.Frontiers in cellular neuroscience · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Serotonin (5-hydroxytryptamine, 5-HT) signaling is thought to modulate nervous system development. Genetic and pharmacological studies support the idea that altered 5-HT signaling during development can have enduring consequences on brain function and behavior. Recently, we discovered that 5-HT can modulate thalamic axon guidance in vitro and in vivo. Embryonic thalamic axons transiently express the 5-HT transporter (SERT; Slc6a4) and accumulate 5-HT, suggesting that the SERT activity of these axons may regulate 5-HT-modulated guidance cues. We tested whether pharmacologically blocking SERT using selective 5-HT reuptake inhibitors (SSRIs) would impact the action of 5-HT on thalamic axon responses to netrin-1 in vitro. Surprisingly, we observed that two high-affinity SSRIs, racemic citalopram ((RS)-CIT) and paroxetine, affect the outgrowth of embryonic thalamic axons, but differ with respect to their dependence on SERT blockade. Using a recently developed 'citalopram insensitive' transgenic mouse line and in vitro pharmacology, we show that the effect of (RS)-CIT effect is SERT independent, but rather arises from R-CIT activation of the orphan sigma-1 receptor(σ1, Oprs1). Our results reveal a novel σ1 activity in modulating axon guidance and a 5-HT independent action of a widely prescribed SSRI. By extension, (RS)-CIT and possibly other structurally similar SSRIs may have other off-target actions that can impact neural development and contribute to therapeutic efficacy or side effects.
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