Enhanced expression of dopamine D₁ and glutamate NMDA receptors in dopamine D₄ receptor knockout mice

Author： Gan Lu Falzone Tomas Zhang Kehong Rubinstein Marcelo Baldessarini Ross Tarazi Frank

ISSN： 0895-8696

Source： Journal of Molecular Neuroscience, Vol.22, Iss.3, 2004-10, pp. : 167-177

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Abstract

Expression of dopamine ([DA] D₁ and D₂) and glutamate ([Glu]), (N-methyl-d-aspartic acid [NMDA], α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], and kanaic acid [KA]) receptor types were analyzed autoradiographically in forebrain regions of D₄ receptor knockout mice and their wild-type controls. Selective radioligand binding to D₄ receptors was virtually absent in D₄ receptor knockout mouse brain in contrast to significant specific D₄ binding in forebrain tissue of wild-type controls. Labeling of D₁ receptors was significantly increased in nucleus accumbens (NAc; 39%) and caudate putamen (CPu; 42%) of D₄-knockout mice vs wild-type controls. In addition, NMDA receptor labeling was significantly increased in NAc (31%), CPu (40%), and hippocampal CA₁ (21%) and CA₃ (25%) regions of D₄ knockouts vs wild-type controls. No changes in D₂, AMPA or KA receptors were found. The findings suggest that D₁, D₄, and NMDA receptors might interact functionally and that developmental absence of D₄ receptors might trigger compensatory mechanisms that enhance expression of D₁ receptors in NAc and CPu, and NMDA receptors in NAc, CPu, and hippocampus. The findings also encourage cautious interpretation of results in knockout mice with targeted absence of specific genes, as complex adaptive changes not directly related to the missing gene might contribute to physiological and behavioral responses.