ArticleProceedings of the National Academy of Sciences of the United States of America2011
Transgenic elimination of high-affinity antidepressant and cocaine sensitivity in the presynaptic serotonin transporter.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study.PloS one · 2012Trial
- Striatal serotonin transporter gain-of-function in L-DOPA-treated, hemi-parkinsonian rats.Brain research · 2023Article
- Synaptic mechanism underlying serotonin modulation of transition to cocaine addiction.Science (New York, N.Y.) · 2021Article
- Inflammation-Induced Histamine Impairs the Capacity of Escitalopram to Increase Hippocampal Extracellular Serotonin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Blockade of the 5-HT transporter contributes to the behavioural, neuronal and molecular effects of cocaine.British journal of pharmacology · 2017Article
- Inhibition of the Serotonin Transporter Is Altered by Metabolites of Selective Serotonin and Norepinephrine Reuptake Inhibitors and Represents a Caution to Acute or Chronic Treatment Paradigms.ACS chemical neuroscience · 2017Article
- Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain.JCI insight · 2017Article
- Essential Contributions of Serotonin Transporter Inhibition to the Acute and Chronic Actions of Fluoxetine and Citalopram in the SERT Met172 Mouse.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy.ACS chemical neuroscience · 2016Article
- A requirement of serotonergic p38α mitogen-activated protein kinase for peripheral immune system activation of CNS serotonin uptake and serotonin-linked behaviors.Translational psychiatry · 2015Article
- Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters.Frontiers in synaptic neuroscience · 2015Article
- The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse.Psychopharmacology · 2014Article
- Mice genetically depleted of brain serotonin do not display a depression-like behavioral phenotype.ACS chemical neuroscience · 2014Article
- Cocaine modulates mammalian circadian clock timing by decreasing serotonin transport in the SCN.Neuroscience · 2014Article
- Stereoselective inhibition of serotonin transporters by antimalarial compounds.Neurochemistry international · 2014Article
- Genetic background modulates phenotypes of serotonin transporter Ala56 knock-in mice.Molecular autism · 2013Article
- The mPer2 clock gene modulates cocaine actions in the mouse circadian system.Behavioural brain research · 2013Article
- A dialogue between the immune system and brain, spoken in the language of serotonin.ACS chemical neuroscience · 2013Review
- The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders.Frontiers in pharmacology · 2013Article
- The SSRI citalopram affects fetal thalamic axon responsiveness to netrin-1 in vitro independently of SERT antagonism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Serotonin [i.e., 5-hydroxytryptamine (5-HT)]-targeted antidepressants are in wide use for the treatment of mood disorders, although many patients do not show a response or experience unpleasant side effects. Psychostimulants, such as cocaine and 3,4-methylenedioxymethamphetamine (i.e., "ecstasy"), also impact 5-HT signaling. To help dissect the contribution of 5-HT signaling to the actions of these and other agents, we developed transgenic mice in which high-affinity recognition of multiple antidepressants and cocaine is eliminated. Our animals possess a modified copy of the 5-HT transporter (i.e., SERT, slc6a4) that bears a single amino acid substitution, I172M, proximal to the 5-HT binding site. Although the M172 substitution does not impact the recognition of 5-HT, this mutation disrupts high-affinity binding of many competitive antagonists in transfected cells. Here, we demonstrate that, in M172 knock-in mice, basal SERT protein levels, 5-HT transport rates, and 5-HT levels are normal. However, SERT M172 mice display a substantial loss of sensitivity to the selective 5-HT reuptake inhibitors fluoxetine and citalopram, as well as to cocaine. Through a series of biochemical, electrophysiological, and behavioral assays, we demonstrate the unique properties of this model and establish directly that SERT is the sole protein responsible for selective 5-HT reuptake inhibitor-mediated alterations in 5-HT clearance, in 5-HT1A autoreceptor modulation of raphe neuron firing, and in behaviors used to predict the utility of antidepressants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.