Literature DB >> 17449106

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

Theresa Currier Thomas1, 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.   

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.

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Year:  2007        PMID: 17449106      PMCID: PMC2699616          DOI: 10.1016/j.jneumeth.2007.03.009

Source DB:  PubMed          Journal:  J Neurosci Methods        ISSN: 0165-0270            Impact factor:   2.390


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