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Addiction Propensity After Prenatal Ethanol Exposure

Shen | Haj-Dahmane | Dlugos
Researchers will study prenatal exposure to ethanol and how that might alter brain mechanisms that influence addiction.

In the current investigation, Dr. Roh-Yu Shen and her research team will extend previous research in which she and Dr. Samir Haj-Dahmane found that prenatal ethanol exposure results in a persistent increase in glutamate synaptic transmission in dopamine (DA) neurons located in the ventral tegmental area (VTA), an effect thought to be a critical cellular mechanism for addiction. The team will use a multidisciplinary approach to further characterize the detailed cellular/molecular mechanims of these effects. Specifically, they will seek to confirm whether prenatal ethanol exposure leads to an increased expression of GluR2-lacking AMPA receptors. They will also investigate how prenatal ethanol exposure induces a blockade of endocannabinoid (eCB)-mediated long-term depression (LTD). Lastly, they will investigate if increased glutamate synaptic transmission mediated by these two cellular mechanisms in VTA DA neurons indeed leads to increased addiction propensity in prenatal ethanol exposed animals. The results generated from the proposed studies will have important implications in understanding the cellular/molecular mechanisms mediating prenatal ethanol exposure-induced increase in addiction propensity; help clarify the complex eCB signaling mechanisms within the mesolimbic/mesocortical DA systems; and may have broad impact beyond fetal alcohol spectrum disorders (FASD). Increased addiction propensity caused by other conditions such as prenatal psychostimulant or stress exposure also alters the function of DA systems, raising the possibility that a common brain mechanism mediates increased addiction propensity. The results from this investigation may provide insights to a common brain mechanism mediating increased addiction propensity and the prevention of addiction in general. Consultants on the study include Dr. Jerry Richards and Dr. Paul Vezina, University of Chicago.

Principal Investigator
Roh-Yu Shen, PhD
Research Institute on Addictions

Co-Investigators
Samir Haj-Dahmane, PhD
Research Institute on Addictions

Cynthia Dlugos, PhD
Department of Pathology and Anatomical Sciences
University at Buffalo

Funding Agency
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Grant Number
R01-AA019482

Dates
2010-2017