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

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

Open access
Ralph, Rebecca J., Varty, Geoffrey B., Kelly, Michele A., Wang, Yan-Min, Caron, Marc G., Rubinstein, Marcelo, Grandy, David K., Low, Malcolm J. +1 more·1999·The Journal of Neuroscience

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1523/jneurosci.19-11-04627.1999

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Studies in mice indicate that administration of direct-acting DA agonists such as apomorphine and indirect DA agonists such as cocaine disrupt PPI primarily via D1 receptors, whereas D2 receptors seem to modulate amphetamine-induced PPI deficits.

    “Studies in mice have indicated that administration of direct-acting DA agonists (such as apomorphine) and indirect DA agonists (such as cocaine) to mice disrupt PPI primarily via D1 receptors [369], whereas D2 receptors seem to modulate amphetamine-induced PPI deficits [370].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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)
Venue
The Journal of Neuroscience
Published
1999-06-01
Volume
19
Issue
11
Pages
4627-4633
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review