The Selective Bromodomain and Extra-Terminal Domain (BET) Inhibitor RVX-208 Reduces Cocaine-Seeking Behaviour and Alters Proteomic Pathways in the Nucleus Accumbens.

ABSTRACT: Bromodomain and extra terminal domain (BET) epigenetic 'reader' proteins are key regulators of both behavioural and molecular responses to cocaine. In substance use disorder (SUD) models, BET function has primarily been investigated using small molecule inhibitors that prevent both bromodomains of BET proteins from interacting with acetylated histones. Although these inhibitors have been shown to be effective in SUD models, the potential adverse effects of pan-BET inhibition may restrict translational applications. Recently, RVX-208, a clinically tested and domain-selective BET inhibitor, was found to reduce cocaine conditioned responses and cocaine-induced gene expression in the nucleus accumbens (NAc), while avoiding the learning and memory impairments associated with pan-BET inhibitors.

SUBMITTER: Sacko TJ 

PROVIDER: S-EPMC12783071 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature