Perhaps the best predictor of ethanol abuse in adolescence is prior fetal exposure. Further, there is an inverse correlation between the age of first experience and the likelihood of developing continued abuse. So, how does fetal exposure alter the acceptability of ethanol to adolescents? How does subsequent adolescent experience, following the fetal exposure, increase adult acceptance? Our novel central hypothesis is that fetal experience-induced plasticity, in response to ethanol, induces developmental changes in one or more of the chemosensory systems involved in the preference for ethanol odor and the perception of ethanol's flavor (the integration of odor, taste and somatosensation): thereby contributing to the risk of initial ethanol ingestion and continued adolescent abuse. We also propose that further ethanol experience during adolescence augments and/or perpetuates the chemosensory effects of fetal exposure, resulting in persistence into adulthood. This proposition is supported by our prior studies and compelling PRELIMINARY DATA demonstrating that clinically relevant fetal exposure to ethanol results in: (1) a tuned neural and behavioral olfactory response to ethanol odor and enhanced ethanol intake in the early postnatal animal that persists into adolescence, yet is absent in adults;(2) enhanced taste-mediated orosensory responsiveness to ethanol in adolescent animals that, in parallel with the olfactory system response, is absent in adults;and (3) that adolescent re-exposure augments the olfactory behavioral response resulting from the prior fetal experience. Our work reveals two chemosensory mechanisms by which fetal exposure enhances ethanol preference and intake. Our long-range goal is to understand how fetal and adolescent ethanol experience impacts the behavioral response to ethanol odor, the perception of ethanol's flavor and the acceptance of the drug;and to understand the chemosensory mechanisms underlying these effects. Applying behavioral, neurophysiologic and anatomical methods, the objectives of this proposal are to determine the impact of fetal and adolescent ethanol experience on adolescent: (1) olfactory system function and ethanol intake;(2) taste-mediated orosensory responses to (and flavor perception of) ethanol and its component qualities (sweet, bitter and irritancy);and (3) the persistence of these effects into adulthood. We will determine whether the neurophysiologic and anatomical effects mediate the behavioral response of the animal. This research is significant - it is expected to: advance our understanding of factors contributing to the initiation of ethanol ingestion and preference during adolescence, and the clinical progression into adult abuse (The Alcoholism Generator)] facilitate the development and testing of preventive and therapeutic strategies;and establish a chemosensory related conceptual framework of fetal and adolescent exposure with broad importance for child development, drug abuse, and environmental health and safety.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA017823-05
Application #
8537098
Study Section
Special Emphasis Panel (ZAA1-BB)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$140,916
Indirect Cost
$28,142
Name
State University of NY, Binghamton
Department
Type
DUNS #
090189965
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

Showing the most recent 10 out of 109 publications