Epigenetic Modifications as Novel Targets for Drug Addiction
Pp. 26-42 (17)
Candace R. Lewis and Michael F. Olive
Drug addiction is a chronic relapsing disorder characterized by maladaptive
patterns of cognition and behavior related to drug use, which are thought to arise from
long term changes in the neural circuitries underlying reward, motivation, affect,
learning and memory, and executive function. Recently, a large body of evidence has
been accumulated showing that epigenetic mechanisms such as DNA methylation and
histone modification are involved in drug-induced maladaptive neural plasticity.
Epigenetics not only provides a novel avenue for examining the molecular mechanisms
underlying interactions between inheritable vulnerabilities and environmental factors
that contribute to addiction and relapse, but also provides novel potential
pharmacological targets for the treatment of addiction. In this chapter, we begin by
introducing relevant epigenetic mechanisms that modulate gene transcription. We then
review and summarize the existing literature on epigenetic changes that occur after
acute and chronic exposure to or self-administration of alcohol, psychostimulants,
opiates, and nicotine, and studies examining the effects of manipulation of epigenetic
processes in reward-related brain regions on addiction-like behaviors. We also discuss
the possible implications of epigenetic factors as predictors of addiction vulnerability
prior to drug exposure. Finally, we will review findings from preclinical studies on the
effects of pharmacological modifiers of epigenetic processes on addiction-related
behaviors, and discuss the advantages and disadvantages of developing novel
epigenetic-based CNS therapeutics for the treatment of addiction.
Drug addiction, epigenetics, gene expression, psychostimulants,
alcohol, nicotine, opiates.
Arizona State University, Tempe, AZ 950 S McAllister Ave., Tempe, AZ 85287, USA.