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Genetic or pharmacological inactivation of the dopamine D 1 receptor differentially alters the expression of regulator of G‐protein signalling (Rgs) transcripts
Author(s) -
Stanwood Gregg D.,
Parlaman Joshua P.,
Levitt Pat
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04970.x
Subject(s) - nucleus accumbens , dopamine , biology , striatum , in situ hybridization , forebrain , rgs2 , dopamine receptor , regulator of g protein signaling , regulator , prenatal cocaine exposure , medium spiny neuron , neuroscience , gene expression , microbiology and biotechnology , medicine , endocrinology , g protein , signal transduction , gene , genetics , gtpase activating protein , central nervous system , offspring , prenatal exposure , pregnancy
Dysregulation of dopamine (DA) receptor signalling induces specific changes in behaviour, neuronal circuitry and gene expression in the mammalian forebrain. In order to better understand signalling adaptations at the molecular level, we used high‐density oligonucleotide microarrays (Codelink Mouse 20K) to define alterations in the expression of transcripts encoding regulator of G‐protein coupled receptor signalling in dopamine D 1 receptor knockout mice ( Drd1a ‐KO). Regulator of G‐protein signalling ( Rgs ) 2 , Rgs4 , and Rgs9 were significantly decreased in the striatum (STR) of Drd1a ‐KO mice. These changes were confirmed by in situ hybridization, and were also observed in the nucleus accumbens (NAc). In contrast, analysis of the medial frontal cortex (MFC) revealed a significant decrease in Rgs17 expression exclusively, and a modest up‐regulation of Rgs5 transcript. The expression of these gene products were not significantly altered in the dopamine‐poor visual cortex (VC). The Drd1a ‐KO mouse, and a rabbit model of in utero cocaine exposure, in which D 1 R signalling is permanently reduced, possess analogous morphological and functional alterations in dopamine‐modulated brain circuits; thus we also examined long‐lasting changes in RGS transcript expression following prenatal exposure to cocaine. In sharp contrast to the Drd1a ‐KO, Rgs2 and Rgs4 were unchanged, and Rgs9 and Rgs17 transcripts were increased in prenatal cocaine‐exposed progeny. These data suggest that an absolute absence of D 1 R signalling ( Drd1a ‐KO) and hypomorphic D 1 R signalling (prenatal cocaine) produce common alterations in neuronal morphology, but distinct outcomes in molecular neuroadaptations.