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• W2012304911 startingPage "823" @default.
• W2012304911 abstract "Our knowledge about genes involved in the control of basal motor activity that may contribute to the pathology of the hyperactivity disorders, e.g., attention deficit hyperactivity disorder (ADHD), is limited. Disruption of monoamine neurotransmitter signaling through G protein-coupled receptors (GPCR) is considered to be a major contributing factor to the etiology of the ADHD. Genetic association evidence and functional data suggest that regulators of G protein signaling proteins of the R7 family (R7 RGS) that form obligatory complexes with type 5 G protein beta subunit (Gβ5) and negatively regulate signaling downstream from monoamine GPCRs may play a role in controlling hyperactivity.To test this hypothesis, we conducted behavioral, pharmacological, and neurochemical studies using a genetic mouse model that lacked Gβ5, a subunit essential for the expression of the entire R7 RGS family.Elimination of Gβ5-RGS complexes led to a striking level of hyperactivity that far exceeds activity levels previously observed in animal models. This hyperactivity was accompanied by motor learning deficits and paradoxical behavioral sensitization to a novel environment. Neurochemical studies indicated that Gβ5-RGS-deficient mice had higher sensitivity of inhibitory GPCR signaling and deficits in basal levels, release, and reuptake of dopamine. Surprisingly, pharmacological treatment with monoamine reuptake inhibitors failed to alter hyperactivity. In contrast, blockade of NMDA receptors reversed the expression of hyperactivity in Gβ5-RGS-deficient mice.These findings establish that Gβ5-RGS complexes are critical regulators of monoamine-NMDA receptor signaling cross-talk and link these complexes to disorders that manifest as hyperactivity, impaired learning, and motor dysfunctions." @default.
• W2012304911 created "2016-06-24" @default.
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• W2012304911 date "2011-07-16" @default.
• W2012304911 modified "2023-10-04" @default.
• W2012304911 title "Gβ5-RGS complexes are gatekeepers of hyperactivity involved in control of multiple neurotransmitter systems" @default.
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• W2012304911 doi "https://doi.org/10.1007/s00213-011-2409-y" @default.
• W2012304911 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3260372" @default.
• W2012304911 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21766168" @default.
• W2012304911 hasPublicationYear "2011" @default.
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