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

Research output: Contribution to journalArticlepeer-review

26 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
Pages (from-to)306-314
Number of pages9
JournalJournal of Neuroscience Methods
Volume166
Issue number2
DOIs
StatePublished - Nov 30 2007

Keywords

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

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