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)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA019925-05
Application #
8706667
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Regunathan, Soundar
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705
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
Spear, Linda Patia; Swartzwelder, H Scott (2014) Adolescent alcohol exposure and persistence of adolescent-typical phenotypes into adulthood: a mini-review. Neurosci Biobehav Rev 45:1-8
Klein, Rebecca C; Saini, Shyla; Risher, M-Louise et al. (2014) Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice. PLoS One 9:e94071
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
Fleming, Rebekah L; Li, Qiang; Risher, Mary-Louise et al. (2013) Binge-pattern ethanol exposure during adolescence, but not adulthood, causes persistent changes in GABAA receptor-mediated tonic inhibition in dentate granule cells. Alcohol Clin Exp Res 37:1154-60
Acheson, Shawn K; Bearison, Craig; Risher, M Louise et al. (2013) Effects of acute or chronic ethanol exposure during adolescence on behavioral inhibition and efficiency in a modified water maze task. PLoS One 8:e77768
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
Fleming, Rebekah L; Acheson, Shawn K; Moore, Scott D et al. (2012) In the rat, chronic intermittent ethanol exposure during adolescence alters the ethanol sensitivity of tonic inhibition in adulthood. Alcohol Clin Exp Res 36:279-85
Fleming, Rebekah L; Acheson, Shawn K; Moore, Scott D et al. (2011) GABA transport modulates the ethanol sensitivity of tonic inhibition in the rat dentate gyrus. Alcohol 45:577-83