Evidence map›Paper›PMID 25609168›Full record

ArticleScience translational medicine2015

Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism.

Olga Peñagarikano, María T Lázaro, Xiao-Hong Lu, Aaron Gordon, Hongmei Dong, Hoa A Lam, Elior Peles, Nigel T Maidment, Niall P Murphy, X William Yang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
214citing papers in PubMed, 2 pooled it
57.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

214 citing papers in PubMed, 2 syntheses or guidelines pooled it, 376 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Oxytocin increases eye gaze in schizophrenia.Schizophrenia research · 2019
    Trial
  5. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Trial
  6. Gut microbes · 2026
    Article
  7. Article
  8. Overview of the DREADDs chemogenetics and the patent landscape of their actuators.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  9. Lasting effects of early-life oxytocin treatment on LTP and episodic memory in a mouse model of Fragile X syndrome.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  10. Lower Striatal and Cortical Calretinin Interneuron Density Associated With Altered Social Behavior in Cntnap2 Knockout Mice.Autism research : official journal of the International Society for Autism Research · 2026
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Astrocytes mediate a positive feedback loop for oxytocin.bioRxiv : the preprint server for biology · 2026
    Article
  17. Review
  18. Review
  19. Article
  20. Article

154 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Olga PeñagarikanoProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
María T LázaroProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xiao-Hong LuCenter for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Aaron GordonDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Hongmei DongProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Hoa A LamDepartment of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Elior PelesDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Nigel T MaidmentDepartment of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Niall P MurphyDepartment of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
X William YangCenter for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Peyman GolshaniProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Integrative Center for Learning and Memory, University of California, Los Angeles, Los Angeles, CA 90095, USA. West Los Angeles VA Medical Center, Los Angeles, CA 90073, USA.
Daniel H GeschwindProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA. Center for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. dhg@ucla.edu.
University of California, Los Angeles · USWeizmann Institute of Science · IL

Funding

Understanding Repetitive Behavior in AutismP50HD055784 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOOKHEIMER, SUSAN Y · 2007 to 2021
$32.0M
A Comprehensive Approach to Identification of Autism Susceptibility GenesR01MH081754 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2008 to 2012
$14.6M
Conditional Mouse Models: Non-cell-antonomous Toxicities in Huntington's DiseaseR01NS049501 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2004 to 2014
$3.8M
Inhibitory neuron circuit organization and function in prefrontal cortex.R01MH105427 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI GOLSHANI, PEYMAN, XU, XIANGMIN · 2015 to 2019
$2.3M
Optogenetic treatment of social behavior in autismR01MH101198 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOLSHANI, PEYMAN · 2013 to 2017
$2.0M
Role of three novel CAMs in myelinating gliaR01NS050220 · NINDS · WEIZMANN INSTITUTE OF SCIENCE · PI PELES, ELIOR · 2005 to 2015
$1.6M
Validating NT17 Dependent Mechanisms in Huntington's Disease SuppressionR01NS074312 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2011 to 2014
$1.4M
NICHD NIH HHS 1P50-HD055784-01NICHD NIH HHS P50 HD055784NIMH NIH HHS 5R01-MH081754-04NIMH NIH HHS R01 MH081754NIMH NIH HHS R01 MH081754-02RNIMH NIH HHS R01 MH101198NIMH NIH HHS R01 MH105427NINDS NIH HHS NS50220NINDS NIH HHS R01 NS049501NINDS NIH HHS R01 NS050220NINDS NIH HHS R01 NS074312
6 · The paper itself

Abstract

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit.

Indexed as

Social BehaviorAnimalsAnimals, NewbornAutistic DisorderBehavior, AnimalDisease Models, AnimalHumansMembrane ProteinsMice, KnockoutMice, Mutant StrainsNerve Tissue ProteinsNeuronsOxytocinParaventricular Hypothalamic NucleusCNTNAP2 protein, mouseMembrane ProteinsNerve Tissue ProteinsOxytocin

Identifiers

PMID25609168
PMCPMC4498455
OpenAlexW2097364496

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.