Fetal ethanol exposure is highly predictive of ethanol abuse in adolescence, and there is an inverse correlation between the age of first experience and the likelihood of continued abuse. How does fetal exposure alter adolescent ethanol acceptability? How does adolescent re-exposure increase adult acceptance? Are the consequences of fetal and adolescent exposure distinct? The fiavor attributes (smell, taste and oral irritation) of ethanol are important determinants of acceptance. We hypothesize that fetal ethanol exposure induces developmental changes in the neural systems involved in the perception and acceptability of ethanol's flavor, thereby increasing the risk of initial ingestion and continued adolescent abuse. Further, adolescent experience with ethanol augments the fetal effect and/or perpetuates the ethanol-induced changes into adulthood. This proposition is supported by our prior studies and compelling preliminary data demonstrating that fetal ethanol exposure: (1) reduces the peripheral neural taste response to quinine (a surrogate for ethanol's bitter taste) and (2) decreases the expression of bitter (T2r) and oral irritation (Trp) receptor genes fundamental to ethanol flavor perception and intake in adolescent rats. We also find that binge ethanol exposure in naive adolescent rats yields similar results to the prenatal T2r findings. Our long-range goal is to apply an understanding of these cellular processes to the development of clinical treatments and strategies. Applying behavioral, genomic and neurophysiologic methods, the objectives of this proposal are to understand mechanistically: (A) the ontogeny of the fetal exposure effect on oro-sensory receptor gene expression and whether the observed effects differ between fetal and adolescent exposure;(B) whether adolescent behavioral responses (following fetal exposure) are mediated by alterations in receptor gene expression;and (C) whether adolescent re-exposure augments the behavioral and receptor response to fetal exposure and/or perpetuates them into adulthood. We will also determine how alterations in the peripheral neural responses to ethanol and stimuli representing its component qualities (bitter, sweet and irritancy) parallel the foregoing behavioral and genomic effects.

Public Health Relevance

Environmental exposures can alter patterns of gene expression in the developing fetus, yielding changes in neural development and function. Our proposal addresses epigenetic chemosensory mechanisms by which maternal ethanol use can be transferred to offspring, and via which, the adolescent system is primed to have the effects of fetal exposure augmented and/or preserved into adulthood. Our studies will provide results within a clinically relevant framework related to adolescent ethanol intake behavior and its progression.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
2P50AA017823-06
Application #
8599913
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
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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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