How stress and anxiety and chronic excessive drinking are related – at the level of genes and molecules – will be the focus of a new $25 million multicenter project funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
Wake Forest University School of Medicine will anchor a consortium of research that will take place at eight centers around the country. Kathleen A. Grant, Ph.D., professor of physiology and pharmacology, is the director of the consortium, known as the Integrative Neuroscience Initiative on Alcohol (INIA).
“Stress causes anxiety, and we know that anxiety is directly related to alcohol abuse,” Grant said. “We know far less about the brain mechanisms that underlie the stress effects, at the molecular and system levels.”
Excessive alcohol use, while it seems to relieve some of the anxiety brought on by stress, can cause an imbalance in brain chemistry that can lead to further alcohol abuse, Grant explained. This is where genetics come into play, she said. It is possible that inherited anxiety traits influence the way that an individual responds both to stress and to the effect of alcohol.
“Depending on the individual,” Grant said, “chronic alcohol consumption itself can produce a state of chronic stress.” Genetic theories will be tested using “knockout mice,” in which suspected genes are removed from one generation to the next, as well as monkeys that model a certain phenotype, or set of genetic characteristics.
In addition to the sophisticated animal models, the consortium will use a full range of modern research tools, including positron emission tomography (PET), magnetic resonance imaging (MRI), and DNA hybridization arrays, which are used to compare the genes of different animals.
“We want to explore all facets of the interactions that influence the relationship between stress, anxiety and alcohol abuse – from molecules to behavior,” Grant said.
INIA grants to Wake Forest this year cover five projects and total more than $1.5 million. Related individual grants total about $1.9 million. Total direct funding for alcohol research at Wake Forest this year tops $6.4 million.
“Wake Forest is becoming a premier alcohol research center,” Grant said. “We’re building ourselves into a position where we’ll be able to lead the country in this kind of research.”
The effect of early childhood stress on alcohol abuse later in life is the subject of another new study by David P. Friedman, Ph.D., professor of physiology and pharmacology. “Studies of adult alcoholics suggest that stress occurring while they were children may have increased their vulnerability to alcohol abuse and alcoholism later in life,” Friedman said.
“Indeed, the response to stress is mediated by neurochemical and endocrine systems that are also influenced by alcohol. This study will examine the effects of early childhood stress on drinking behavior and on the neurochemistry and stress hormone responses of animals given free access to alcohol.”
Allyson J. Bennett, Ph.D., assistant professor of physiology and pharmacology and of pediatrics, will study the effects of teen-age binge drinking on learning, neuroendochrine development, behavior, and the inclination to drink too much in adulthood.
Bennett cited statistics showing that half of all American eighth-graders and 80 percent of high school students said they had had at least one drink of alcohol in the past month. Fourteen percent of eighth-graders and 35 percent of high school males (28 percent for females) said they had engaged in binge drinking -- defined as at least four to five drinks in a 24-hour period.
"Adolescent drinking and binge drinking is a huge public health issue," Bennett said. "We need to know what the effect of adolescent binge drinking is on the brain and on behavior, so that we can help teenagers and young adults make good health decisions, but also so that we can truly understand any long-term effects of that alcohol exposure."
Bennett''s research will use male monkeys that present a good model of human development through adolescence into adulthood. The monkeys have a clearly defined adolescence, but one that much shorter than humans''. The monkeys will be divided into three groups -- one that is allowed to binge drink as adolescents, a second that is not allowed to drink until adulthood, and a third group that never drinks.
All three groups will begin with a year of baseline testing: physiological measurements, cognitive testing, and behavioral observations. Changes will be measured throughout a five-year period.
A key segment of Bennett''s research will test whether the animals who binge drank as adolescents are more likely to drink excessively as adults than animals who didn''t start drinking until adulthood. Then, following a period of abstinence, both groups will be given the opportunity to relapse. "Treatments for relapse are one of the most critical areas of research," Bennett said. "We need to develop better therapies."
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