Cited by 271Neurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatmentNeuroscience and Neuropharmacology Research

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Prepulse Inhibition Deficits and Perseverative Motor Patterns in Dopamine Transporter Knock-Out Mice: Differential Effects of D1 and D2 Receptor Antagonists

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Ralph, Rebecca J., Paulus, Martin P., Fumagalli, Fabio, Caron, Marc G., Geyer, Mark A.·2001·The Journal of Neuroscience

DOI 10.1523/jneurosci.21-01-00305.2001PMC PMC6762423

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Abstract

Dopamine is known to regulate several behavioral phenomena, including sensorimotor gating and aspects of motor activity. The roles of dopamine D1 and D2 receptors in these behaviors have been documented in the rat literature, but few reports exist on their role in mice. We used dopamine transporter (DAT) (−/−) mice to examine the behavioral consequences of a chronically hyperdopaminergic state, challenging them with the preferential dopamine D2 receptor antagonist raclopride and D1 receptor antagonist SCH23390. At baseline, DAT (−/−) mice exhibited deficient sensorimotor gating as measured by prepulse inhibition (PPI) of the startle response, exhibited nonfocal perseverative patterns of locomotion, and were hyperactive in a novel environment. Pretreatment with raclopride significantly increased PPI in the DAT (−/−) mice, whereas SCH23390 had no significant effect. Blockade of D2 receptors did not affect the predominantly straight patterns of motor behavior produced by the DAT (−/−) mice, but antagonism of D1 receptors significantly attenuated the perseverative patterns, producing more of a meandering behavior seen in the DAT (+/+) control mice. Both D1 and D2 receptor antagonists decreased the hyperactivity seen in the DAT (−/−) mice. These findings support the role of the D2, but not the D1, receptor in the modulation of PPI in mice. Furthermore, D1 receptor activation appears to be the critical substrate for the expression of perseverative patterns of motor behavior, whereas both D1 and D2 receptors appear to regulate the amount of motor activity.

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Authors: Ralph, R. J., Paulus, M. P., Fumagalli, F., Caron, M. G., & Geyer, M. A.
Affiliations: University of California San Diego (US)
University of Milan (IT)
Howard Hughes Medical Institute (US)
ORCID: Paulus, Martin P.
Fumagalli, Fabio
Caron, Marc G.
Geyer, Mark A.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2001-01-01
Volume: 21
Issue: 1
Pages: 305-313
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.21-01-00305.2001
PMC: PMC6762423
OpenAlex: W2133067994
Cited by: 271
References: 31
Citations by year: 2026: 4 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 9 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 13 · 2015: 12 · 2014: 15 · 2013: 12 · 2012: 11
FWCI: 5.16
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
U.S. Department of Veterans Affairs
National Institutes of Health (5r01da011277-03)
National Institute of Mental Health (F31-MH-12806, MH42228, R37MH042228, R01MH042228, R01MH061326)
National Institute on Drug Abuse (DA 02925, R01DA002925, DA11277)
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: prepulse inhibition, sensorimotor gating, dopamine transporter knockout mice, dopamine D1 receptor, dopamine D2 receptor, dopamine D1 receptor antagonist, dopamine D2 receptor antagonists, raclopride, SCH 23390, locomotor hyperactivity, hyperdopaminergic state
MeSH terms: Animals, Behavior, Animal, Benzazepines, Carrier Proteins, Female, Heterozygote, Homozygote, Hyperkinesis, Injections, Intraperitoneal, Injections, Subcutaneous, Male, Membrane Glycoproteins, Motor Activity, Movement Disorders, Nerve Tissue Proteins, Neural Inhibition, Sex Factors, Reflex, Startle, Receptors, Dopamine D1, Receptors, Dopamine D2, Mice, Knockout, Dopamine Antagonists, Raclopride, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins, Mice, Dopamine D2 Receptor Antagonists

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Prepulse Inhibition Deficits and Perseverative Motor Patterns in Dopamine Transporter Knock-Out Mice: Differential Effects of D1 and D2 Receptor Antagonists

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