ArticleBritish journal of pharmacology2013
Blockade of the high-affinity noradrenaline transporter (NET) by the selective 5-HT reuptake inhibitor escitalopram: an in vivo microdialysis study in mice.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 32 citations in OpenAlex.
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- Ethanol induced antidepressant-like effect in the mouse forced swimming test: modulation by serotonergic system.Psychopharmacology · 2017Article
- A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- In vivo properties of KNT-127, a novel δ opioid receptor agonist: receptor internalization, antihyperalgesia and antidepressant effects in mice.British journal of pharmacology · 2014Article
- The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse.Psychopharmacology · 2014Article
- Voltammetric and mathematical evidence for dual transport mediation of serotonin clearance in vivo.Journal of neurochemistry · 2014Article
- 5-HT₂A receptor inactivation potentiates the acute antidepressant-like activity of escitalopram: involvement of the noradrenergic system.Experimental brain research · 2013Article
- Antidepressant activity: contribution of brain microdialysis in knock-out mice to the understanding of BDNF/5-HT transporter/5-HT autoreceptor interactions.Frontiers in pharmacology · 2013Article
- Selective deletion of forebrain glycogen synthase kinase 3β reveals a central role in serotonin-sensitive anxiety and social behaviour.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2012Article
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeEscitalopram, the S(+)-enantiomer of citalopram is the most selective 5-HT reuptake inhibitor approved. Although all 5-HT selective reuptake inhibitors (SSRIs) increase extracellular levels of 5-HT ([5-HT](ext)). some also enhance, to a lesser extent, extracellular levels of noradrenaline ([NA](ext)). However, the mechanisms by which SSRIs activate noradrenergic transmission in the brain remain to be determined. EXPERIMENTAL APPROACH: This study examined the effects of escitalopram, on both [5-HT](ext) and [NA](ext) in the frontal cortex (FCx) of freely moving wild-type (WT) and mutant mice lacking the 5-HT transporter (SERT(-/-)) by using intracerebral microdialysis. We explored the possibilities that escitalopram enhances [NA](ext), either by a direct mechanism involving the inhibition of the low- or high-affinity noradrenaline transporters, or by an indirect mechanism promoted by [5-HT](ext) elevation. The forced swim test (FST) was used to investigate whether enhancing cortical [5-HT](ext) and/or [NA](ext) affected the antidepressant-like activity of escitalopram. KEY
resultsIn WT mice, a single systemic administration of escitalopram produced a significant increase in cortical [5-HT](ext) and [NA](ext). As expected, escitalopram failed to increase cortical [5-HT](ext) in SERT(-/-) mice, whereas its neurochemical effects on [NA](ext) persisted in these mutants. In WT mice subjected to the FST, escitalopram increased swimming parameters without affecting climbing behaviour. Finally, escitalopram, at relevant concentrations, failed to inhibit cortical noradrenaline and 5-HT uptake mediated by low-affinity monoamine transporters. CONCLUSIONS AND IMPLICATIONS: These experiments suggest that escitalopram enhances, although moderately, cortical [NA](ext) in vivo by a direct mechanism involving the inhibition of the high-affinity noradrenaline transporter (NET).
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