This grant application is in response to NIAAA announcement RFA-AA-10-006 entitled """"""""Neurobiology of adolescent drinking in adulthood"""""""" (NADIA), and is a part of a Consortium of researchers investigating broad spectrum behavioral and neuropathological changes during adulthood after adolescent ethanol (EtOH) exposure. There is high prevalence of binge drinking among adolescents. Adolescence is a critical period for brain development that is particularly vulnerable to the neurotoxic effects of EtOH. Although some adolescent and adult alcoholics show deficits in attention and increased impulsivity, it is not known whether these behavioral alterations preceded or are the result of alcohol abuse. Increased impulsivity during adolescence in general may partially be attributed to hypersensitivity of the reward system in the adolescent brain, a system whose functioning may be altered by excessive alcohol drinking in adolescence. In addition, considering that the reward circuitry also regulates responses to stress, underage drinking may also alter responses to stressors. Finally, underage drinking is likely to alter dopaminergic (DA) and serotonergic (5- HT) transmitter systems involved in impulsivity, reward processes, and stress responsivity. Adolescent intermittent ethanol (AIE) exposure in rats models several aspects of underage binge drinking in humans. The long-term effects of adolescent EtOH exposure on attention, impulsivity, brain reward function and responses to stress, as well as the effects of alcohol challenges on these behaviors during adulthood remain largely unknown. The proposed studies will fill this gap in knowledge by investigating the long-term impact of AIE on attention and impulsivity (Aim 1), impulsive and risky decision-making (Aim 2), brain reward function and stress responsiveness (Aim 3), and the neurochemical changes in DA and 5-HT transmission likely to be involved in these behavioral alterations (Aim 4) in rats. It is hypothesized that AIE will result in a neuropathology of the DA and 5-HT corticolimbic and striatal brain areas that will manifest itself as impaired attention, increased impulsivity, poor decision-making, reward deficits, and altered responses to stressors during adulthood. These findings may lead to the discovery of behavioral and neurochemical targets for the discovery of treatments to assist people affected by underage drinking who exhibit poor decision-making, highly impulsive behaviors, mental health problems, such as depression/anhedonia, and/or excessive alcohol drinking in adulthood.

Public Health Relevance

Adolescent exposure to alcohol may induce severe long-term brain damage that may result in profound behavioral and cognitive deficits that impair day-to-day function in adulthood. Further, such abnormalities may lead to alcoholism and exacerbate responses to stressors. This project will identify potential behavioral and neuropathological mechanisms in adulthood resulting from alcohol exposure in adolescence, and thus lead to the design.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAA1-DD (11))
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Grandison, Lindsey
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Boutros, Nathalie; Der-Avakian, Andre; Semenova, Svetlana et al. (2016) Risky choice and brain CRF after adolescent ethanol vapor exposure and social stress in adulthood. Behav Brain Res 311:160-166
Boutros, Nathalie; Semenova, Svetlana; Markou, Athina (2014) Adolescent intermittent ethanol exposure diminishes anhedonia during ethanol withdrawal in adulthood. Eur Neuropsychopharmacol 24:856-64
Boutros, Nathalie; Semenova, Svetlana; Liu, Wen et al. (2014) Adolescent intermittent ethanol exposure is associated with increased risky choice and decreased dopaminergic and cholinergic neuron markers in adult rats. Int J Neuropsychopharmacol 18:
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Risher, Mary-Louise; Fleming, Rebekah L; Boutros, Nathalie et al. (2013) Long-term effects of chronic intermittent ethanol exposure in adolescent and adult rats: radial-arm maze performance and operant food reinforced responding. PLoS One 8:e62940
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