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 language | English |
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Pages (from-to) | 306-314 |
Number of pages | 9 |
Journal | Journal of Neuroscience Methods |
Volume | 166 |
Issue number | 2 |
DOIs | |
State | Published - Nov 30 2007 |
Bibliographical note
Funding Information:These studies were supported by USPHS grants MH070840, P20 RR020171, DA017186, MH066393, and MH067497.
Keywords
- ADHD
- Chronoamperometry
- Dopamine
- Dopamine receptors
- Nucleus accumbens core
- Striatum
- d-Amphetamine
ASJC Scopus subject areas
- General Neuroscience