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

First Author  Thomas TC Year  2007
Journal  J Neurosci Methods Volume  166
Issue  2 Pages  306-14
PubMed ID  17449106 Mgi Jnum  J:136872
Mgi Id  MGI:3797255 Doi  10.1016/j.jneumeth.2007.03.009
Citation  Thomas TC, et al. (2007) Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release. J Neurosci Methods 166(2):306-14
abstractText  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.
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