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NIAAA P01

NIAAA P01

Translational Studies on Early Life Stress and Vulnerability to Alcohol Addiction

Director: Jeff Weiner, PhD
Scientific Director: Brian McCool, PhD

Early life stress (ELS) refers to severe and/or chronic trauma, environmental or social deprivation, or neglect, occurring either in prenatal or early postnatal life.  ELS is now well recognized as a major risk factor for a diverse range of adverse outcomes across the lifespan, including cognitive, behavioral and psychiatric domains. Notably, ELS is known to substantially increase risk of internalizing disorders (e.g. anxiety, depression) as well as vulnerability to drug and alcohol abuse. Preclinical studies in humans have provided a wealth of information regarding the behavioral and biological consequences associated with ELS.  Unfortunately, many questions remain unanswered, particularly with respect to the specific neurobiological mechanisms linking ELS and increased vulnerability to addictive disorders. To that end, many animal models of ELS have been developed and results from these studies have contributed substantively to our understanding of the behavioral and biological consequences of ELS. The goal of this P01 project is to employ well-established preclinical human and animal research models to conduct integrated, translational studies directed at identifying specific behavioral and neurobiological correlates through which ELS increases risk of alcohol use disorder later in life. 

This P01 employs a Center-like structure that includes highly integrated rodent, non-human primate, and human projects. An administrative core provides the infrastructure and support needed to ensure the success of the research. This core also actively promotes new translational alcohol research by creating translational research training and outreach activities related to the scientific goals of the P01. 

This project takes advantage of the numerous strengths that characterize the alcohol research community at Wake Forest School of Medicine. First, we are a highly collaborative translational alcohol research unit. This unit has been working together to establish parallel models to study the relationship between ELS and alcoholism in humans, non-human primates, and rodents. Second, the projects outlined in this application represent the fruit of these collaborations, leverage the strengths and advantages of each species, and build on substantive preliminary and published data obtained through prior programmatic grant support from NIAAA. Collectively, these studies focus on the specific hypotheses that ELS results in enduring increases in a diverse array of behaviors that contribute to increased vulnerability to alcohol addiction.  Experiments in the non-human primate and rodent models will also directly assess the hypothesis that ELS results in dysregulation of neurophysiological mechanisms that may represent synaptic correlates of addiction vulnerability.  Finally, each of the projects will test interventional approaches aimed at mitigating the adverse behavioral and neurobiological effects of ELS. The ultimate goal of these integrated, translational studies is to accelerate the transition from laboratory discovery to new and more effective treatment of alcohol use disorder.  The goals and objectives of this project will be achieved through the following specific aims:

Specific Aim 1:  Translational neurobehavioral studies on early life stress and vulnerability to alcohol use disorder.
Three highly integrated, multidisciplinary research projects, using human, non-human primate, and rodent models, will test hypotheses directed at identifying behavioral and neurobiological substrates linking early life stress and increased addiction vulnerability.  Each project will also examine interventions targeted at reducing the deleterious behavioral and neurobiological effects of early life stress.  

Specific Aim 2: Administrative core for the translational research projects.
To facilitate the scientific goals and objectives of this project, this P01 will establish an administrative core that will provide infrastructure and support for each of the research projects.  This core will also actively promote new translational alcohol research outreach and training opportunities at Wake Forest School of Medicine.  A major emphasis will be to promote scientific integration across projects to maximize the likelihood of proceeding from benchside discovery to the development of novel treatment strategies for alcohol addiction.

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