In humans, a strong association between anxiety and alcohol use has been reported among adolescents. Enhanced vulnerability to both anxiety and alcohol use disorders in adolescence is frequently associated with prenatal alcohol exposure, however, the mechanisms contributing to this enhanced vulnerability in adolescents prenatally exposed to alcohol remain poorly understood. A main limitation of the human data is that much of the research has involved self-report questionnaires, which limits causal interpretation of the results and does not permit systematic manipulation of critical variables, due to ethical considerations. Therefore, animal models are of particular importance. The proposed studies will use a simple rat model of social anxiety induced by acute prenatal ethanol exposure to assess responsiveness to social stressors and ethanol sensitivity in adolescents with the social inhibition and/or social avoidance phenotype. Offspring tested in adulthood will be included to assess persistence of alterations in stress responsiveness and ethanol sensitivity. The proposed research will address the following aims: (1) test whether the social avoidance phenotype induced by prenatal ethanol exposure is associated with enhanced stress responsiveness;(2) test whether (a) sensitivity to ethanol-induced social facilitation and ethanol-induced anxiolysis and (b) intake of ethanol under social circumstances are enhanced following prenatal ethanol exposure;(3) test whether the social avoidance phenotype induced by prenatal ethanol exposure is associated with alterations in structural plasticity in the neurocircuitry implicated in stress and anxiety. These studies will provide critical new information regarding mechanisms involved in vulnerability to affective and alcohol use disorders among adolescents exposed to alcohol prenatally. Understanding of these mechanisms is essential for creating new prevention and intervention strategies as well as new approaches to pharmacological treatment of alcohol use disorders during adolescence.

Public Health Relevance

Prenatal alcohol exposure increases the risk of anxiety and alcohol use disorders later in life, conditions with considerable effects on health, society and the economy. The proposed work will expand our understanding of mechanisms leading to anxiety and alcohol use disorders in adolescents prenatally exposed to alcohol and will help to more effectively prevent prenatal alcohol exposure and treat its consequences.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
2P50AA017823-06
Application #
8601381
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
State University of NY, Binghamton
Department
Type
DUNS #
City
Binghamton
State
NY
Country
United States
Zip Code
13902
Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence (2017) A cross-sectional comparison of ethanol-related cytokine expression in the hippocampus of young and aged Fischer 344 rats. Neurobiol Aging 54:40-53
Fernandez, Gina M; Lew, Brandon J; Vedder, Lindsey C et al. (2017) Chronic intermittent ethanol exposure leads to alterations in brain-derived neurotrophic factor within the frontal cortex and impaired behavioral flexibility in both adolescent and adult rats. Neuroscience 348:324-334
Vore, Andrew S; Doremus-Fitzwater, Tamara; Gano, Anny et al. (2017) Adolescent Ethanol Exposure Leads to Stimulus-Specific Changes in Cytokine Reactivity and Hypothalamic-Pituitary-Adrenal Axis Sensitivity in Adulthood. Front Behav Neurosci 11:78
Deak, Terrence; Kudinova, Anastacia; Lovelock, Dennis F et al. (2017) A multispecies approach for understanding neuroimmune mechanisms of stress. Dialogues Clin Neurosci 19:37-53
Gano, Anny; Pautassi, Ricardo Marcos; Doremus-Fitzwater, Tamara L et al. (2017) Conditioned effects of ethanol on the immune system. Exp Biol Med (Maywood) 242:718-730
Akinmboni, T O; Davis, N L; Falck, A J et al. (2017) Excipient exposure in very low birth weight preterm neonates. J Perinatol :
Lovelock, D F; Deak, T (2017) Repeated exposure to two stressors in sequence demonstrates that corticosterone and paraventricular nucleus of the hypothalamus interleukin-1? responses habituate independently. J Neuroendocrinol 29:
Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence (2016) Sustained alterations in neuroimmune gene expression after daily, but not intermittent, alcohol exposure. Brain Res 1646:62-72
Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I (2016) Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats. Behav Brain Res 310:11-9
Fernandez, Gina M; Stewart, William N; Savage, Lisa M (2016) Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure. PLoS One 11:e0149987

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