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Cited by 104Neurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatmentNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.

The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice

Barr, Alasdair M, Lehmann-Masten, Virginia, Paulus, Martin, Gainetdinov, Raul R, Caron, Marc G, Geyer, Mark A·2004·Neuropsychopharmacology
DOI 10.1038/sj.npp.1300343
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Abstract

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT(2A) receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT(2A) receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.

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Metadata

Authors
Barr, A. M., Lehmann-Masten, V., Paulus, M., Gainetdinov, R. R., Caron, M. G., & Geyer, M. A.
Affiliations
  • Scripps Research Institute (US)
  • University of California San Diego (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Geyer, Mark A
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2003-11-05
Volume
29
Issue
2
Pages
221-228
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/sj.npp.1300343
OpenAlex
W2123933616
Cited by
103
References
56
Citations by year
2026: 2 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 7
FWCI
2.32
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • National Institute of Mental Health (MH60451, MH61326, R01MH061326, P50MH060451)
  • National Institute on Drug Abuse (DA 02925, R01DA002925)
  • NIH Clinical Center
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
M100907, 5-HT2A receptor antagonist, dopamine transporter knockout mice, hyperdopaminergic state, prepulse inhibition, sensorimotor gating, locomotor activity, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder
MeSH terms
Acoustic Stimulation, Analysis of Variance, Animals, Mental Disorders, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Fluorobenzenes, Inhibition, Psychological, Locomotion, Membrane Glycoproteins, Nerve Tissue Proteins, Piperidines, Reflex, Acoustic, Reversal Learning, Spatial Behavior, Mice, Knockout, Gait Disorders, Neurologic, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins, Mice, Serotonin 5-HT2 Receptor Antagonists

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