Project Summary/Abstract
It is well established that drug-induced alterations to gene expression contribute to the development of drug-
seeking behaviors. For instance, both acute and chronic exposure to cocaine increases histone acetylation within
and significantly alters transcriptional profiles within the nucleus accumbens (NAc). Our lab has demonstrated
that HDAC3, a histone deacetylase enzyme, within the NAc negatively regulates cocaine-induced changes in
histone acetylation, gene expression, and memory formation. However, it is unknown whether cocaine alters
HDAC3-mediated transcriptional changes underlying reward-associated behavior in a sex-dependent manner.
In a recent study, our lab identified Gilz (glucocorticoid-induced leucine zipper) as an HDAC3 target gene that
may be critical for memory formation. Gilz is an X-chromosome linked gene which may provide novel insight into
sex-differences observed in response to cocaine exposure. I have collected preliminary data suggesting Gilz
positively regulates reinstatement of previously extinguished cocaine-seeking behavior, perhaps through
transcription-dependent mechanisms of synaptic plasticity. However, the precise role of Gilz in reinstatement
remains unknown, as does whether these observations are consistent across both sexes. The experiments
proposed in this application will allow me to test the overall hypothesis that Gilz acts in the NAc to regulate
transcription underlying cellular and behavioral responses to cocaine.
