The Class I HDAC, HDAC1 is also involved in the cellular responses to chronic psychostimulant exposure: it binds to Δ FosB and facilitates repression of downstream target genes [59]. An example of this occurs at the c-fos promoter, where ΔFosB accumulates after a chronic course of psychostimulants to desensitize its activation to subsequent drug exposure. Prior administration of the HDAC inhibitor, sodium butyrate, or local genetic deletion of the HDAC1 gene from the NAc, increases c-fos induction despite previous treatment with chronic psychostimulants [59]. This ΔFosB/HDAC1-mediated desensitization of c-fos is part of the “molecular switch” whereby acute Fos family proteins are gradually replaced by ΔFosB during a course of chronic drug exposure. Further studies are needed to identify other genes that are repressed via this unique mechanism.
