Cited by 176Neurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatmentNeuroscience and Neuropharmacology Research

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The Dopamine D2, but not D3or D4, Receptor Subtype is Essential for the Disruption of Prepulse Inhibition Produced by Amphetamine in Mice

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Ralph, Rebecca J., Varty, Geoffrey B., Kelly, Michele A., Wang, Yan-Min, Caron, Marc G., Rubinstein, Marcelo, Grandy, David K., Low, Malcolm J., Geyer, Mark A.·1999·The Journal of Neuroscience

DOI 10.1523/jneurosci.19-11-04627.1999PMC PMC6782596

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Abstract

Brain dopamine (DA) systems are involved in the modulation of the sensorimotor gating phenomenon known as prepulse inhibition (PPI). The class of D2-like receptors, including the D2, D3, and D4 receptor subtypes, have all been implicated in the control of PPI via studies of DA agonists and antagonists in rats. Nevertheless, the functional relevance of each receptor subtype remains unclear because these ligands are not specific. To determine the relevance of each receptor subtype, we used genetically altered strains of “knock-out” mice lacking the DA D2, D3, or D4 receptors. We tested the effects of each knock-out on both the phenotypic expression of PPI and the disruption of PPI produced by the indirect DA agonist d-amphetamine (AMPH). No phenotypic differences in PPI were observed at baseline. AMPH significantly disrupted PPI in the D2 (+/+) mice but had no effect in the D2 (−/−) mice. After AMPH treatment, both DA D3 and D4 receptor (+/+) and (−/−) mice had significant disruptions in PPI. These findings indicate that the AMPH-induced disruption of PPI is mediated via the DA D2 receptor and not the D3 or D4 receptor subtypes. Uncovering the neural mechanisms involved in PPI will further our understanding of the substrates of sensorimotor gating and could lead to better therapeutics to treat gating disorders, such as schizophrenia.

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Authors: Ralph, R. J., Varty, G. B., Kelly, M. A., Wang, Y.-M., Caron, M. G., Rubinstein, M., Grandy, D. K., Low, M. J., & Geyer, M. A.
Affiliations: University of California San Diego (US)
Vollum Institute (US)
Howard Hughes Medical Institute (US)
Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
Oregon Health & Science University (US)
ORCID: Varty, Geoffrey B.
Kelly, Michele A.
Caron, Marc G.
Rubinstein, Marcelo
Grandy, David K.
Low, Malcolm J.
Geyer, Mark A.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1999-06-01
Volume: 19
Issue: 11
Pages: 4627-4633
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.19-11-04627.1999
PMC: PMC6782596
OpenAlex: W2100216270
Cited by: 174
References: 38
Citations by year: 2026: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 6
FWCI: 5.38
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 183 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
National Alliance for Research on Schizophrenia and Depression
National Institute of Mental Health (K05-MH01228, F31MH012086)
National Institute on Drug Abuse
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: prepulse inhibition, sensorimotor gating, dopamine D2 receptor, dopamine D3 receptor, dopamine D4 receptor, amphetamine, receptor knockout mice, schizophrenia
MeSH terms: Acoustic Stimulation, Amphetamine, Animals, Mice, Mutant Strains, Neural Inhibition, Receptors, Dopamine, Reflex, Startle, Dopamine Agents, Receptors, Dopamine D2, Mice, Knockout, Receptors, Dopamine D3, Receptors, Dopamine D4, Mice

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The Dopamine D2, but not D3or D4, Receptor Subtype is Essential for the Disruption of Prepulse Inhibition Produced by Amphetamine in Mice

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