Most people in the U.S. begin using alcohol during adolescence. Strikingly, 29% of 12th graders and 42% of college students report having had five or more drinks in a row during the last two weeks, and about 90% of the alcohol consumed by youth under the age of 21 in the U.S. is in the form of 'binge drinks.'This high prevalence of binge drinking occurs at a critical period for brain development that makes the adolescent brain uniquely vulnerable to negative consequences of alcohol exposure. We have consistently found that adolescent rats respond differently to acute ethanol than do adults. And studies in young humans report differential responsiveness to alcohol among children and late adolescents, relative to adults. Similar developmental differences in sensitivity to acute ethanol are found in electrophysiological studies as well in hippocampal and neocortical brain slices. In contrast, little is known about the long-term changes in behavioral or neural function that result from repeated alcohol exposure during adolescence, or about the cellular mechanisms that may underlie them. We have found that intermittent ethanol treatment during adolescence (AIE) blunts the normal maturational increase in sensitivity to ethanol-induced motor impairment in adulthood, and the normal maturational decrease in sensitivity to the acute effects of ethanol on learning. That is, AIE decreases adult sensitivity to the effects of ethanol on motor function, and increases adult sensitivity to ethanol induced learning impairments. We have now collected preliminary data indicating that AIE results in spatial learning impairments and diminished hippocampal long-term potentiation in adult rats. Thus our overall hypothesis is that AIE will alter adult hippocampal function, and learning and memory processes in adulthood. We have designed three sets of experiments to address this hypothesis. We will assess the effects of AIE on learning and memory as well as memory-related hippocampal functions at the circuit and cellular levels, during adulthood. The use of alcohol by adolescents represents a major public health concern with long-lasting impact on health care in the U.S. Recent studies have shown that alcohol affects brain function differently during adolescence than adulthood. However, the more pressing question relates to the possible long-term effects of repeated alcohol exposure during adolescence. The experiments proposed in this application will address this issue.

Public Health Relevance

The use of alcohol by adolescents represents a major public health concern with long-lasting impact on health care in the U.S. Recent studies have shown that alcohol affects brain function differently during adolescence than adulthood. However, the more pressing question relates to the possible long-term effects of repeated alcohol exposure during adolescence. The experiments proposed in this application will address this issue.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA019925-04
Application #
8525262
Study Section
Special Emphasis Panel (ZAA1-DD (11))
Program Officer
Bechtholt-Gompf, Anita
Project Start
2010-09-01
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$276,058
Indirect Cost
$61,227
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Swartzwelder, H S; Park, Maeng-Hee; Acheson, Shawn (2017) Adolescent Ethanol Exposure Enhances NMDA Receptor-Mediated Currents in Hippocampal Neurons: Reversal by Gabapentin. Sci Rep 7:13133
Miller, Kelsey M; Risher, Mary-Louise; Acheson, Shawn K et al. (2017) Behavioral Inefficiency on a Risky Decision-Making Task in Adulthood after Adolescent Intermittent Ethanol Exposure in Rats. Sci Rep 7:4680
Tupler, Larry A; Zapp, Daniel; DeJong, William et al. (2017) Alcohol-Related Blackouts, Negative Alcohol-Related Consequences, and Motivations for Drinking Reported by Newly Matriculating Transgender College Students. Alcohol Clin Exp Res 41:1012-1023
Ruby, Christina L; Palmer, Kaitlyn N; Zhang, Jiawen et al. (2017) Differential Sensitivity to Ethanol-Induced Circadian Rhythm Disruption in Adolescent and Adult Mice. Alcohol Clin Exp Res 41:187-196
Swartzwelder, H Scott; Risher, Mary-Louise; Miller, Kelsey M et al. (2016) Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure. PLoS One 11:e0155951
Swartzwelder, H Scott; Acheson, Shawn K; Miller, Kelsey M et al. (2015) Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers. PLoS One 10:e0140042
Risher, Mary-Louise; Fleming, Rebekah L; Risher, W Christopher et al. (2015) Adolescent intermittent alcohol exposure: persistence of structural and functional hippocampal abnormalities into adulthood. Alcohol Clin Exp Res 39:989-97
Risher, Mary-Louise; Sexton, Hannah G; Risher, W Christopher et al. (2015) Adolescent Intermittent Alcohol Exposure: Dysregulation of Thrombospondins and Synapse Formation are Associated with Decreased Neuronal Density in the Adult Hippocampus. Alcohol Clin Exp Res 39:2403-13
Centanni, Samuel W; Teppen, Tara; Risher, Mary-Louise et al. (2014) Adolescent alcohol exposure alters GABAA receptor subunit expression in adult hippocampus. Alcohol Clin Exp Res 38:2800-8
Swartzwelder, H S; Hogan, A; Risher, M-Louise et al. (2014) Effect of sub-chronic intermittent ethanol exposure on spatial learning and ethanol sensitivity in adolescent and adult rats. Alcohol 48:353-60

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