The overall goal of this research is to expand the investigation of alcohol-induced memory impairments in a rodent model of Alcohol-Related Neurodevelopmental Disorder (ARND). Individuals diagnosed with Fetal Alcohol Syndrome (FAS) or ARND exhibit significant deficits in a variety of memory domains, including explicit, declarative, associative, extinction, and spatial. To date, the study of memory impairments using animal models has focused almost exclusively on tasks that require spatial learning and spatial navigation. The experiments outlined in this research proposal are intended to expand the study of memory deficits by using tasks that have no overt spatial component. We intend to address four specific aims in this research. In all experiments, animals will be administered alcohol during the neonatal period (days 4-9) to model third trimester human exposure.
The first aim i s intended to further explore short- and long-term nonassociative memory deficits by expanding upon our previous work using habituation of the heart rate orienting response. These experiments will address issues of dose-response functions, limited durations of alcohol exposure, and variations in methodology to promote nonassociative learning.
The second aim will examine the relation between nonassociative and associative learning using a Pavlovian fear conditioning procedure and measuring several fear-related conditioned responses (behavior, heart rate, and fear-potentiated startle).
The third aim will expand the study of declarative and explicit memory impairments by investigating alcohol-induced changes in trace conditioning and contextual conditioning. In addition, extinction of the conditioned responses acquired in these associative tasks will be evaluated to increase our understanding of alcohol effects on one type of executive function. Finally, the experiments addressing the last aim are geared toward an initial examination of potential behavioral and pharmacological treatments to ameliorate memory impairments resulting from alcohol exposure. The behavioral training techniques are based on transfer of learning from one situation to another, while the pharmacological treatments will include acute administration of cholinesterase inhibitors or chronic choline supplementation to the diet of the offspring. Collectively, these studies will further our understanding of memory impairments observed in humans with FAS or ARND by using tasks with an animal model that fall outside the realm of explicit spatial learning and memory. The potential for amelioration of these cognitive deficits using both behavioral and pharmacological strategies will provide important information regarding treatment approaches for afflicted individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA015343-04
Application #
7414385
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Matochik, John A
Project Start
2005-05-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
4
Fiscal Year
2008
Total Cost
$101,693
Indirect Cost
Name
College of William and Mary
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
074762238
City
Williamsburg
State
VA
Country
United States
Zip Code
23187
Hunt, Pamela S; Barnet, Robert C (2016) Adolescent and adult rats differ in the amnesic effects of acute ethanol in two hippocampus-dependent tasks: Trace and contextual fear conditioning. Behav Brain Res 298:78-87
Hunt, Pamela S; Barnet, Robert C (2015) An animal model of fetal alcohol spectrum disorder: Trace conditioning as a window to inform memory deficits and intervention tactics. Physiol Behav 148:36-44
Hunt, Pamela S; Jacobson, Sarah E; Kim, Sarah (2014) Supplemental choline does not attenuate the effects of neonatal ethanol administration on habituation of the heart rate orienting response in rats. Neurotoxicol Teratol 44:121-5
Schreiber, William B; Hunt, Pamela S (2013) Deficits in trace fear conditioning induced by neonatal alcohol persist into adulthood in female rats. Dev Psychobiol 55:352-60
Hunt, Pamela S (2012) Supplemental choline during the periweaning period protects against trace conditioning impairments attributable to post-training ethanol exposure in adolescent rats. Behav Neurosci 126:593-8
Spaeth, Andrea M; Barnet, Robert C; Hunt, Pamela S et al. (2010) Adolescent nicotine exposure disrupts context conditioning in adulthood in rats. Pharmacol Biochem Behav 96:501-6
Hunt, Pamela S; Jacobson, Sarah E; Torok, Elena J (2009) Deficits in trace fear conditioning in a rat model of fetal alcohol exposure: dose-response and timing effects. Alcohol 43:465-74
Hunt, Pamela S; Levillain, Mary E; Spector, Bethany M et al. (2009) Post-training ethanol disrupts trace conditioned fear in rats: effects of timing of ethanol, dose and trace interval duration. Neurobiol Learn Mem 91:73-80
Morasch, Katherine C; Hunt, Pamela S (2009) Persistent deficits in heart rate response habituation following neonatal binge ethanol exposure. Alcohol Clin Exp Res 33:1596-604
Hunt, Pamela S; Fanselow, Michael S; Richardson, Rick et al. (2007) Synapses, circuits, and the ontogeny of learning. Dev Psychobiol 49:649-63

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