Drug addiction can be viewed as a stable form of drug-induced neural plasticity, whereby long-lasting changes in gene expression mediate some of the stable behavioral abnormalities that define an addicted state. Our laboratory has focused on transcriptional pathways in addiction, deduced from large RNA-sequencing datasets of RNAs that show altered expression in brain reward regions of mice as a consequence of drug self-administration, withdrawal, and relapse. Activation or induction of certain transcription factors represent homeostatic adaptations that oppose drug action and mediate aspects of drug tolerance and dependence. In contrast, induction of other transcription factors exerts the opposite effect and contributes to sensitized responses to drug exposure. We are also characterizing a range of chromatin mechanisms that act in concert with these transcription factors to control gene expression. These studies are identifying many of the molecular targets of drug self-administration in brain reward regions and the biochemical pathways most prominently affected. Parallel work has focused on homologous regions in the brains of addicted humans examined postmortem. These advances can now be mined to develop improved diagnostic tests and treatments for addictive disorders.
Funded by the National Institute on Drug Abuse