Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli

Stephanie C. Dulawa, David Grandy, Malcolm J. Low, Martin P. Paulus, Mark A. Geyer

    Research output: Contribution to journalArticle

    345 Citations (Scopus)

    Abstract

    The involvement of dopamine neurotransmission in behavioral responses to novelty is suggested by reports that reward is related to increased dopamine activity, that dopamine modulates exploratory behavior in animals, and that Parkinson's disease patients report diminished responses to novelty. Some studies have reported that polymorphisms of the human dopamine D4 receptor (D4R) gene are associated with personality inventory measures of the trait called 'novelty-seeking'. To explore a potential role for the D4R in behavioral responses to novelty, we evaluated D4R-knock-out (D4R-/-) and wild-type (D4R+/+) mice in three approach-avoidance paradigms: the open field, emergence, and novel object tests. These three paradigms differ in the degree to which they elicit approach, or exploratory behavior, and avoidance, or anxiety-related behavior. Thus, we used these three tests to determine whether the D4R primarily influences the exploratory or the anxious component of responses to approach-avoidance conflicts, D4R-/- mice were significantly Jess behaviorally responsive to novelty than D4R+/+ mice in all three tests. The largest phenotypic differences were observed in the novel object test, which maximizes approach behavior, and the smallest phenotypic differences were found in the open field test, which maximizes avoidance behavior. Hence, D4R-/- mice exhibit reductions in behavioral responses to novelty, reflecting a decrease in novelty-related exploration.

    Original languageEnglish (US)
    Pages (from-to)9550-9556
    Number of pages7
    JournalJournal of Neuroscience
    Volume19
    Issue number21
    StatePublished - Nov 1 1999

    Fingerprint

    Dopamine D4 Receptors
    Knockout Mice
    Choice Behavior
    Dopamine
    Exploratory Behavior
    Avoidance Learning
    Personality Inventory
    Animal Diseases
    Reward
    Synaptic Transmission
    Parkinson Disease
    Anxiety
    Genes

    Keywords

    • Anxiety
    • Approach-avoidance
    • D4 receptor
    • Exploration
    • Mice
    • Novelty
    • Open field

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Dulawa, S. C., Grandy, D., Low, M. J., Paulus, M. P., & Geyer, M. A. (1999). Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. Journal of Neuroscience, 19(21), 9550-9556.

    Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. / Dulawa, Stephanie C.; Grandy, David; Low, Malcolm J.; Paulus, Martin P.; Geyer, Mark A.

    In: Journal of Neuroscience, Vol. 19, No. 21, 01.11.1999, p. 9550-9556.

    Research output: Contribution to journalArticle

    Dulawa, SC, Grandy, D, Low, MJ, Paulus, MP & Geyer, MA 1999, 'Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli', Journal of Neuroscience, vol. 19, no. 21, pp. 9550-9556.
    Dulawa SC, Grandy D, Low MJ, Paulus MP, Geyer MA. Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. Journal of Neuroscience. 1999 Nov 1;19(21):9550-9556.
    Dulawa, Stephanie C. ; Grandy, David ; Low, Malcolm J. ; Paulus, Martin P. ; Geyer, Mark A. / Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 21. pp. 9550-9556.
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