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Dopamine D2 receptor signaling in the brain modulates circadian liver metabolomic profiles
Author(s) -
Marlene Cervantes,
Robert W. Lewis,
Maria Agnese Della Fazia,
Emiliana Borrelli,
Paolo SassoneCorsi
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2117113119
Subject(s) - metabolome , dopamine , dopaminergic , biology , circadian rhythm , metabolomics , dopamine receptor , dopamine receptor d2 , medium spiny neuron , circadian clock , signal transduction , endocrinology , medicine , neuroscience , pharmacology , microbiology and biotechnology , striatum , bioinformatics
Significance We analyzed the liver metabolome of mice deficient in the expression of the dopamine D2 receptor (D2R) in striatal medium spiny neurons (iMSN-D2RKO) and found profound changes in the liver circadian metabolome compared to control mice. Additionally, we show activation of dopaminergic circuits by acute cocaine administration in iMSN-D2RKO mice reprograms the circadian liver metabolome in response to cocaine. D2R signaling in MSNs is key for striatal output and essential for regulating the first response to the cellular and rewarding effects of cocaine. Our results suggest changes in dopamine signaling in specific striatal neurons evoke major changes in liver physiology. Dysregulation of liver metabolism could contribute to an altered allostatic state and therefore be involved in continued use of drugs.

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