Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release

Theresa Currier Thomas, Paul J. Kruzich, B. Matthew Joyce, C. R. Gash, Katherine Suchland, Stewart P. Surgener, Erin C. Rutherford, David K. Grandy, Greg A. Gerhardt, Paul E.A. Glaser

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    21 Scopus citations

    Abstract

    Dopamine D4 receptor (D4R) knockout mice (D4R-/-) provided for unique neurochemical studies designed to understand D4R contributions to dopamine (DA) regulation. In this study, post-mortem brain tissue content of DA did not differ between D4R+/+ and D4R-/- mice in the striatum (Str) or nucleus accumbens core (NAc). However, there was a significant decrease (82%) in the content of 3,4-dihydoxyphenylacetic acid (DOPAC), a major metabolite of DA, in the NAc of D4R-/- mice. Microdialysis studies performed in a region of brain spanning of the dorsal Str and NAc showed lower baseline levels of DA and a significant reduction in KCl-evoked overflow of DA in the D4R-/- mice. Baseline extracellular levels of DOPAC and homovanillic acid were also significantly lower in the D4R-/- mice. In vivo chronoamperometric recordings of KCl-evoked release of DA also showed decreased release of DA in the Str and NAc of the D4R-/- mice. These studies demonstrate a role of D4Rs in presynaptic DA regulation and support the hypothesis that alterations in D4Rs may lead to diminished DA function.

    Original languageEnglish (US)
    Pages (from-to)306-314
    Number of pages9
    JournalJournal of Neuroscience Methods
    Volume166
    Issue number2
    DOIs
    StatePublished - Nov 30 2007

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    Keywords

    • ADHD
    • Chronoamperometry
    • Dopamine
    • Dopamine receptors
    • Nucleus accumbens core
    • Striatum
    • d-Amphetamine

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Thomas, T. C., Kruzich, P. J., Joyce, B. M., Gash, C. R., Suchland, K., Surgener, S. P., Rutherford, E. C., Grandy, D. K., Gerhardt, G. A., & Glaser, P. E. A. (2007). Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release. Journal of Neuroscience Methods, 166(2), 306-314. https://doi.org/10.1016/j.jneumeth.2007.03.009