Abstract

Adolescent alcohol abuse is a significant health concern. However, the long-term consequences of adolescent alcohol exposure in animal models have not been extensively examined. Studies from this laboratory demonstrate impaired cortical, hippocampal, and basal forebrain function in adult rats exposed to alcohol during adolescence. These neurophysiological deficits point towards deficits in attention and memory function, which may model those observed in adolescent alcohol abusers. Adolescent N-methyI-D-asparate (NMDA) receptor systems are likely to play a key role in ethanol's unique effects on the adolescent due to their increased sensitivity to ethanol. NMDA receptors also play an important role in the regulation of attention and memory function in brain regions, which have been demonstrated to be impaired by adolescent alcohol exposure. The principal hypothesis underlying this proposal is: Ethanol exerts its unique effects on the adolescent by inducing a lasting upregulation of NMDA systems. As a consequence, the development of ethanol withdrawal and neurodegeneration is enhanced in adolescents. Furthermore, this NMDA upregulation persists into adulthood and contributes to the long-term neurophysiological and cognitive deficits observed following adolescent alcohol exposure. The studies proposed in this application examine the development of ethanol dependence and the lasting neurobehavioral consequences of adolescent ethanol exposure using behavioral, cellular/histochemical, and neurophysiological techniques. The goals of this application are accomplished through the following specific aims:
AIM 1. To investigate the development of ethanol dependence during adolescence.
AIM 2. To investigate the behavioral consequences of adolescent ethanol exposure, with a focus on sustained attention and working memory.
AIM 3 : To investigate the neurochemical substrates underlying the lasting neurobehavioral consequences of adolescent ethanol exposure, with a focus on NMDA systems

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
3R01AA014339-02S1
Application #
7106043
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Witt, Ellen
Project Start
2004-09-28
Project End
2009-06-30
Budget Start
2005-08-05
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$86,769
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Walker, Brendan M; Drimmer, David A; Walker, Jennifer L et al. (2010) Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains. Alcohol 44:487-93
Crabbe, John C; Bell, Richard L; Ehlers, Cindy L (2010) Human and laboratory rodent low response to alcohol: is better consilience possible? Addict Biol 15:125-44
Pian, J P; Criado, J R; Milner, R et al. (2010) N-methyl-D-aspartate receptor subunit expression in adult and adolescent brain following chronic ethanol exposure. Neuroscience 170:645-54
Ehlers, Cindy L; Criado, Jose R (2010) Adolescent ethanol exposure: does it produce long-lasting electrophysiological effects? Alcohol 44:27-37
Criado, Jose R; Ehlers, Cindy L (2010) Event-related oscillations in the parietal cortex of adult alcohol-preferring (P) and alcohol-nonpreferring rats (NP). Alcohol 44:335-42
Criado, Jose R; Ehlers, Cindy L (2010) Effects of adolescent ethanol exposure on event-related oscillations (EROs) in the hippocampus of adult rats. Behav Brain Res 210:164-70
Criado, J R; Ehlers, C L (2009) Event-related oscillations as risk markers in genetic mouse models of high alcohol preference. Neuroscience 163:506-23
Pian, Jerry P; Criado, Jose R; Walker, Brendan M et al. (2009) Milk consumption during adolescence decreases alcohol drinking in adulthood. Pharmacol Biochem Behav 94:179-85
Walker, Brendan M; Ehlers, Cindy L (2009) Appetitive motivational experience during adolescence results in enhanced alcohol consumption during adulthood. Behav Neurosci 123:926-35
Walker, Brendan M; Ehlers, Cindy L (2009) Age-related differences in the blood alcohol levels of Wistar rats. Pharmacol Biochem Behav 91:560-5

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