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.

ABSTRACT: 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 generalize

SUBMITTER: Schroeder FA 

PROVIDER: S-EPMC2746694 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature