Cited by 102Obsessive-Compulsive Spectrum DisordersNeurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatment

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Chronic Reductions in Serotonin Transporter Function Prevent 5-HT1B-Induced Behavioral Effects in Mice

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Shanahan, Nancy A., Holick Pierz, Kerri A., Masten, Virginia L., Waeber, Christian, Ansorge, Mark, Gingrich, Jay A., Geyer, Mark A., Hen, Rene, Dulawa, Stephanie C.·2009·Biological Psychiatry

DOI 10.1016/j.biopsych.2008.09.026PMC PMC2674010

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Abstract

Background Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts, images, or impulses and/or repetitive stereotypical behavior. Obsessive-compulsive disorder patients exhibit reduced prepulse inhibition (PPI) and symptom exacerbation after challenge with 5-HT1B receptor agonists. Recently, gain-of-function alleles of the serotonin transporter (5-HTT) have been associated with OCD. We tested the hypothesis that reducing 5-HTT function chronically, either genetically or via serotonin reuptake inhibitor (SRI) treatment, attenuates PPI deficits and perseverative hyperlocomotion induced by 5-HT1B agonists in mice.Methods Mice received subchronic or chronic pretreatment with the SRI fluoxetine and acute treatment with RU24969 (5-HT1A/1B agonist) or 8-OH-DPAT (5-HT1A agonist) and were assessed for PPI, locomotor activity, and spatial patterns of locomotion. The same measures were evaluated in 5-HTT wild-type (WT), heterozygous (HT), and knockout (KO) mice after RU24969 treatment. The effects of WAY100635 (5-HTA antagonist) or GR127935 (5-HT1B/D antagonist) pretreatment on RU24969-induced effects were evaluated. Finally, 5-HT1B binding and functional coupling were assessed in 5-HTT-WT, -HT, and -KO mice, and normal fluoxetine-treated mice.Results Chronic, but not subchronic, fluoxetine treatment prevented RU24969-induced PPI deficits and perseverative hyperlocomotion. These RU24969-induced effects were mediated via 5-HT1B and not 5-HT1A receptors. 5-HTT-KO mice showed no effects of RU24969, and 5-HTT-HT mice exhibited intermediate phenotypes. 5-HT1B binding and functional coupling were reduced in the globus pallidus and substantia nigra of 5-HTT-KO mice.Conclusions Our results demonstrate that chronic, but not subchronic, fluoxetine treatment and 5-HTT knockout robustly attenuate 5-HT1B agonist-induced PPI deficits and perseverative hyperlocomotion. These results may have implications for the etiology and treatment of OCD.

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Self-citation
Additional file 3 of Distinct behavioral traits and associated brain regions in mouse models for obsessive–compulsive disorder
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Additional file 2 of Distinct behavioral traits and associated brain regions in mouse models for obsessive–compulsive disorder
Chen, X., Yue, J., Luo, Y., Huang, L., Li, B., & Wen, S. (2021) · Figshare · doi:10.6084/m9.figshare.14615396
Additional file 1 of Distinct behavioral traits and associated brain regions in mouse models for obsessive–compulsive disorder
Chen, X., Yue, J., Luo, Y., Huang, L., Li, B., & Wen, S. (2021) · Figshare · doi:10.6084/m9.figshare.14615390
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Contribution des récepteurs 5-HT4 à la motivation et la prise de décision de manger
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Mécanismes du maintien de l'hyper-réactivité noradrénergique et sérotoninergique induite par l'exposition répétée à l'amphétamine
Bobadilla, A. (2014) · theses.fr (ABES) · doi:10.70675/786a53c8zca3bz47f9zb0b3ze3c8efd7157d

Authors: Shanahan, N. A., Holick Pierz, K. A., Masten, V. L., Waeber, C., Ansorge, M., Gingrich, J. A., Geyer, M. A., Hen, R., & Dulawa, S. C.
Affiliations: University of California San Diego (US)
Harvard University (US)
Columbia University (US)
University of Chicago (US)
Corresponding author: Dulawa, Stephanie C.
ORCID: Waeber, Christian
Ansorge, Mark
Gingrich, Jay A.
Geyer, Mark A.
Dulawa, Stephanie C.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2009-03
Volume: 65
Issue: 5
Pages: 401-408
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2008.09.026
PMC: PMC2674010
OpenAlex: W2058616430
Cited by: 102
References: 60
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 13 · 2020: 6 · 2019: 8 · 2018: 3 · 2017: 1 · 2016: 8 · 2015: 5 · 2014: 5 · 2013: 9 · 2012: 8
FWCI: 9.29
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (K01MH071555, R01MH079424)
National Institute on Drug Abuse (DA 02925, T32DA07255-15, R01DA002925, T32DA007255)
National Institute of Neurological Disorders and Stroke (R01NS049263, R21NS052195)
Topics: Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: serotonin transporter, 5-HT1B receptor, obsessive-compulsive disorder, prepulse inhibition, fluoxetine, serotonin reuptake inhibitors, 8-OH-DPAT, 5-HT1A receptor, globus pallidus, substantia nigra, gain-of-function alleles
MeSH terms: Animals, Female, Fluoxetine, Globus Pallidus, Indoles, Mice, Inbred BALB C, Motor Activity, Oxadiazoles, Piperazines, Pyridines, Reflex, Startle, Substantia Nigra, 8-Hydroxy-2-(di-n-propylamino)tetralin, Mice, Knockout, Receptor, Serotonin, 5-HT1B, Serotonin Plasma Membrane Transport Proteins, Mice, Serotonin 5-HT1 Receptor Agonists, Serotonin 5-HT1 Receptor Antagonists

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Chronic Reductions in Serotonin Transporter Function Prevent 5-HT1B-Induced Behavioral Effects in Mice

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