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.
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