Drug-induced activation of dopamine D(1) receptor signaling and inhibition of class I/II histone deacetylase induce chromatin remodeling in reward circuitry and modulate cocaine-related behaviors
Authors
Schroeder, Frederick AlbertPenta, Krista L.
Matevossian, Anouch
Jones, Sara R.
Konradi, Christine L.
Tapper, Andrew R.
Akbarian, Schahram
Student Authors
Frederick SchroederUMass Chan Affiliations
Tapper LabDepartment of Psychiatry
Brudnick Neuropsychiatric Research Institute
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2008-02-22Keywords
Brain; Chromatin Assembly and Disassembly; Cocaine; Histone Deacetylase Inhibitors; Receptors, Dopamine D1Life Sciences
Medicine and Health Sciences
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Chromatin remodeling, including histone modification, is involved in stimulant-induced gene expression and addiction behavior. To further explore the role of dopamine D(1) receptor signaling, we measured cocaine-related locomotor activity and place preference in mice pretreated for up to 10 days with the D(1) agonist SKF82958 and/or the histone deacetylase inhibitor (HDACi), sodium butyrate. Cotreatment with D(1) agonist and HDACi significantly enhanced cocaine-induced locomotor activity and place preference, in comparison to single-drug regimens. However, butyrate-mediated reward effects were transient and only apparent within 2 days after the last HDACi treatment. These behavioral changes were associated with histone modification changes in striatum and ventral midbrain: (1) a generalized increase in H3 phosphoacetylation in striatal neurons was dependent on activation of D(1) receptors; (2) H3 deacetylation at promoter sequences of tyrosine hydroxylase (Th) and brain-derived neurotrophic factor (Bdnf) in ventral midbrain, together with upregulation of the corresponding gene transcripts after cotreatment with D(1) agonist and HDACi. Collectively, these findings imply that D(1) receptor-regulated histone (phospho)acetylation and gene expression in reward circuitry is differentially regulated in a region-specific manner. Given that the combination of D(1) agonist and HDACi enhances cocaine-related sensitization and reward, the therapeutic benefits of D(1) receptor antagonists and histone acetyl-transferase inhibitors (HATi) warrant further investigation in experimental models of stimulant abuse.Source
Neuropsychopharmacology. 2008 Nov;33(12):2981-92. Epub 2008 Feb 20. Link to article on publisher's site
DOI
10.1038/npp.2008.15Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32903PubMed ID
18288092Related Resources
ae974a485f413a2113503eed53cd6c53
10.1038/npp.2008.15