The major goal of this P01 is to leverage institutional strengths in human, non-human primate, and rodent alcohol research to conduct translational studies directed at understanding the complex relationships between early life stress and vulnerability to alcohol use disorders. This project will take advantage of a highly productive and successful translational alcohol research unit at WFHS that was recently established with NIAAA programmatic grant support. This research unit will employ multidisciplinary approaches to identify enduring behavioral and neurobiological consequences of early life stress, determine how these alterations contribute to excessive alcohol drinking behaviors, and test novel interventional strategies that may be effective at alleviating addiction vulnerability associated with early life stress. The overarching hypothesis is that early life stress results in long lastin behavioral alterations that contribute to an increased risk of alcohol addiction (with a focus on anxiety-like behaviors). It is also hypothesized that these behavioral alterations are mediated, in part, by dysregulatlon of dopamine signaling and glutamate receptor function and plasticity in the nucleus accumbens. Aspects of these hypotheses will be evaluated in human subjects with and without a history of early life stress and with well-established non-human primate and rodent models of early life stress. This P01 will employ a Center-like structure that will include highly integrated rodent, non-human primate, and human projects. An administrative core will provide the infrastructure and support needed to ensure the success of the research. This core will also actively promote new translational alcohol research through a pilot project program and create new translational research training and outreach activities related to the scientific goals f the P01. A major emphasis will be to promote scientific integration across projects to maximize the likelihood of proceeding from benchside discovery to novel treatment strategies for alcohol addiction.

Public Health Relevance

The proposed studies outline a multidisciplinary, translational research initiative that will bring together human, non-human primate, and rodent alcohol researchers to address complex and unresolved questions regarding the neurobiological mechanisms that link early life stress and alcohol addiction. These translational studies will shed new light on important behavioral phenotypes associated with early environmental stress, their association with excessive alcohol drinking, and specific neurobiological mechanisms that may underlie these relationships. This project will also explore novel interventional strategies that may mitigate the increased addiction vulnerability associated with early-life stress.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Program Projects (P01)
Project #
1P01AA021099-01
Application #
8268634
Study Section
Special Emphasis Panel (ZAA1-GG (21))
Program Officer
Grandison, Lindsey
Project Start
2012-09-20
Project End
2017-08-31
Budget Start
2012-09-20
Budget End
2013-08-31
Support Year
1
Fiscal Year
2012
Total Cost
$495,705
Indirect Cost
$160,769
Name
Wake Forest University Health Sciences
Department
Physiology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T et al. (2016) Chronic ethanol self-administration in macaques shifts dopamine feedback inhibition to predominantly D2 receptors in nucleus accumbens core. Drug Alcohol Depend 158:159-63
Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T et al. (2016) Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques. Psychopharmacology (Berl) 233:1435-43
Skelly, M J; Chappell, A M; Ariwodola, O J et al. (2016) Behavioral and neurophysiological evidence that lateral paracapsular GABAergic synapses in the basolateral amygdala contribute to the acquisition and extinction of fear learning. Neurobiol Learn Mem 127:10-6

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