The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice

Rebecca J. Ralph, Geoffrey B. Varty, Michele A. Kelly, Yan Min Wang, Marc G. Caron, Marcelo Rubinstein, David Grandy, Malcolm J. Low, Mark A. Geyer

    Research output: Contribution to journalArticle

    158 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)4627-4633
    Number of pages7
    JournalJournal of Neuroscience
    Volume19
    Issue number11
    StatePublished - Jun 1 1999

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    Amphetamine
    Dopamine
    Dopamine D4 Receptors
    Dopamine D3 Receptors
    Sensory Gating
    Dopamine D2 Receptors
    Dopamine Agonists
    Prepulse Inhibition
    Dextroamphetamine
    Dopamine Antagonists
    Knockout Mice
    Schizophrenia
    Ligands
    Brain

    Keywords

    • Amphetamine
    • Dopamine receptors
    • Genetics
    • Mice
    • Prepulse inhibition
    • Startle

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Ralph, R. J., Varty, G. B., Kelly, M. A., Wang, Y. M., Caron, M. G., Rubinstein, M., ... Geyer, M. A. (1999). The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice. Journal of Neuroscience, 19(11), 4627-4633.

    The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice. / Ralph, Rebecca J.; Varty, Geoffrey B.; Kelly, Michele A.; Wang, Yan Min; Caron, Marc G.; Rubinstein, Marcelo; Grandy, David; Low, Malcolm J.; Geyer, Mark A.

    In: Journal of Neuroscience, Vol. 19, No. 11, 01.06.1999, p. 4627-4633.

    Research output: Contribution to journalArticle

    Ralph, RJ, Varty, GB, Kelly, MA, Wang, YM, Caron, MG, Rubinstein, M, Grandy, D, Low, MJ & Geyer, MA 1999, 'The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice', Journal of Neuroscience, vol. 19, no. 11, pp. 4627-4633.
    Ralph, Rebecca J. ; Varty, Geoffrey B. ; Kelly, Michele A. ; Wang, Yan Min ; Caron, Marc G. ; Rubinstein, Marcelo ; Grandy, David ; Low, Malcolm J. ; Geyer, Mark A. / The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 11. pp. 4627-4633.
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