Study Provides More Evidence of Biologic Basis of Drug Addiction Interview with:

Shelly B. Flagel, PhD Molecular and Behavioral Neuroscience Institute Department of Psychiatry University of Michigan, Ann Arbor, MI 48109

Dr. Shelly B. Flagel

Shelly B. Flagel, PhD
Molecular and Behavioral Neuroscience Institute
Department of Psychiatry
University of Michigan, Ann Arbor, MI 48109 What is the background for this study? What are the main findings?

Dr. Flagel: We used a unique genetic animal model to examine individual differences in addiction liability. This model of selectively bred rat lines allowed us to examine the brains of “addiction-prone” and “addiction-resilient” rats before and after they were exposed to cocaine. I

mportantly, even though all rats were exposed to the same amount of drug, only a certain subset exhibited addiction-like behavior. We focused our neurobiological analyses on two molecules that have been previously implicated in response to drugs of abuse – the dopamine D2 receptor and fibroblast growth factor (FGF2). We examined gene expression and the epigenetic regulation of these molecules and found that low levels of FGF2 in the core of the nucleus accumbens, a brain region known for regulating motivated behavior, may protect individuals from becoming addicted; whereas low levels of D2 in this brain region may predispose individuals to addiction.

Further, this is the first study to show that epigenetic modulation of these molecules may be a predisposing factor and that, the epigenetic regulation of D2 may be especially important in susceptibility to relapse. What should clinicians and patients take away from your report?

Dr. Flagel: This work provides further evidence for a biological basis of addiction, which is important for the public to understand. In addition, it highlights the role of inherited traits and the notion that individual differences in vulnerability to addiction exist and should not be ignored. What recommendations do you have for future research as a result of this study?

Dr. Flagel: The most obvious next steps are to target the epigenetic regulation of molecules like D2 to see if that can affect the propensity for relapse, which we are currently working on. In addition, we will be using these selectively bred rat lines as well as other animal models in combination with broad-based genotyping techniques to uncover other genes that contribute to various facets of drug abuse and addiction. Is there anything else you would like to add?

Dr. Flagel: Here is the link to our website: Thank you for your contribution to the community.


Shelly B. Flagel, Sraboni Chaudhury, Maria Waselus, Rebeca Kelly, Salima Sewani, Sarah M. Clinton,Robert C. Thompson, Stanley J. Watson Jr., and Huda Akil

Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model
PNAS 2016 ; published ahead of print April 25, 2016, doi:10.1073/pnas.1520491113

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Last Updated on April 29, 2016 by Marie Benz MD FAAD