ArticlePsychopharmacology2010
The effects of acute treatment with escitalopram on the different stages of contextual fear conditioning are reversed by atomoxetine.
Article in Psychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The effect of SSRIs on fear learning: a systematic review and meta-analysis.Psychopharmacology · 2023Pooled it
- Sensitivity of [(11)C]ORM-13070 to increased extracellular noradrenaline in the CNS - a PET study in human subjects.Psychopharmacology · 2015Trial
- Sex-specific exploration patterns and noradrenergic modulation in object recognition memory: Role of the perirhinal cortex.Psychopharmacology · 2026Article
- Noradrenaline activation of hippocampal dopamine DProceedings of the National Academy of Sciences of the United States of America · 2022Article
- A Complex Impact of Systemically Administered 5-HT2A Receptor Ligands on Conditioned Fear.The international journal of neuropsychopharmacology · 2021Article
- A retinoraphe projection regulates serotonergic activity and looming-evoked defensive behaviour.Nature communications · 2017Article
- Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function.CNS spectrums · 2016Review
- Acute escitalopram but not contextual conditioning exerts a stronger "anxiogenic" effect in rats with high baseline "anxiety" in the acoustic startle paradigm.Psychopharmacology · 2015Article
- Intraperitoneal sertraline and fluvoxamine increase contextual fear conditioning but are without effect on overshadowing between cues.Pharmacology, biochemistry, and behavior · 2015Article
- Potentiation of GluN2C/D NMDA receptor subtypes in the amygdala facilitates the retention of fear and extinction learning in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Inhibitory networks of the amygdala for emotional memory.Frontiers in neural circuits · 2013Review
- The selective serotonin reuptake inhibitor, escitalopram, enhances inhibition of prepotent responding and spatial reversal learning.Journal of psychopharmacology (Oxford, England) · 2012Article
- Serotonergic modulation of conditioned fear.Scientifica · 2012Review
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleAlthough the antidepressant and anxiolytic effects of selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors are well-documented, less is known about their cognitive effects.
objectiveEscitalopram, a selective serotonin reuptake inhibitor, and atomoxetine, a selective noradrenaline reuptake inhibitor, were used to evaluate the interaction between noradrenergic and serotonergic neurotransmission in the modulation of contextual fear conditioning in rats.
methodsContextual fear-conditioning test was used to investigate the acute effects of escitalopram, alone or in combination with atomoxetine, in different stages of learning and memory in rats. Furthermore, microdialysis in freely moving animals was used to investigate the effect of escitalopram on serotonin, dopamine, and noradrenaline levels in the rat hippocampus.
resultsEscitalopram significantly increased conditioned responses when applied before the acquisition, but decreased responses, when applied before the recall test. When administered during memory consolidation, escitalopram dose-dependently enhanced conditioned responding. These effects were blocked by atomoxetine. Escitalopram (at a dose that affects memory consolidation) increased hippocampal serotonin levels fourfold without changing dopamine or noradrenaline. Atomoxetine, at dose levels that blocked the effects of escitalopram on contextual fear conditioning, increased the extracellular levels of noradrenaline eightfold but did not change dopamine or serotonin. A combined treatment of escitalopram and atomoxetine caused a significant attenuation of escitalopram-induced increase in serotonin levels, while noradrenaline levels were not affected.
conclusionsThese findings indicate that escitalopram affects fear memory in rats, likely modulated by increases in serotonin levels in the brain. This effect is impaired by atomoxetine, probably due to a noradrenaline-mediated decrease in serotonin levels. Further studies are warranted to study the effects of potential differences among antidepressant therapies on long-term cognitive outcomes.
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