University of Kentucky

Poster Title

STUDY 1: Learning and Memory Deficits Are Attenuated by the Nmda Receptor Antagonist, Cp-101,606, in a Rodent Model of Third-Trimester Alcohol Exposure

Institution

University of Kentucky

Abstract

Fetal Alcohol Syndrome (FAS) is the leading preventable cause of mental retardation in the U.S., with estimated costs exceeding eleven billion dollars annually. Hence, there is a great need for interventions capable of lessening the impact of fetal alcohol exposure. Long-term behavioral impairments displayed by children with FAS include a variety of learning and memory deficits. This study used a rodent model of 3rd trimester alcohol exposure to evaluate a pharmacologic intervention designed to reduce such deficits. One mechanism that may be responsible for some of alcohol's damaging effects occurs during alcohol withdrawal when the n-methyl-d-aspartate receptor displays overexcitation resulting in cell death. It was hypothesized that blocking this overexcitation (using CP-101,606 obtained from Pfizer) could reduce excitotoxicity and improve behavioral outcomes. For this 3rd trimester model, rat pups were given alcohol added to a milk solution during the first week after birth. On postnatal day (PND) 8, CP was administered during alcohol withdrawal, producing 5 treatment groups: ALC (6g/kg/day), CP (15mg/kg), ALC+CP and two control groups. Animals were tested on two consecutive days (PND 40-41) in a water maze test assessing spatial learning and memory. While the alcohol-exposed offspring showed deficits on this task, those receiving alcohol + CP performed better than the alcohol-exposed offspring, suggesting that CP-101,606 may be a useful treatment for reducing some damaging effects of fetal alcohol. Although CP appears promising, further investigation is needed to determine its clinical relevance and efficacy in other behavioral deficits.

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STUDY 1: Learning and Memory Deficits Are Attenuated by the Nmda Receptor Antagonist, Cp-101,606, in a Rodent Model of Third-Trimester Alcohol Exposure

Fetal Alcohol Syndrome (FAS) is the leading preventable cause of mental retardation in the U.S., with estimated costs exceeding eleven billion dollars annually. Hence, there is a great need for interventions capable of lessening the impact of fetal alcohol exposure. Long-term behavioral impairments displayed by children with FAS include a variety of learning and memory deficits. This study used a rodent model of 3rd trimester alcohol exposure to evaluate a pharmacologic intervention designed to reduce such deficits. One mechanism that may be responsible for some of alcohol's damaging effects occurs during alcohol withdrawal when the n-methyl-d-aspartate receptor displays overexcitation resulting in cell death. It was hypothesized that blocking this overexcitation (using CP-101,606 obtained from Pfizer) could reduce excitotoxicity and improve behavioral outcomes. For this 3rd trimester model, rat pups were given alcohol added to a milk solution during the first week after birth. On postnatal day (PND) 8, CP was administered during alcohol withdrawal, producing 5 treatment groups: ALC (6g/kg/day), CP (15mg/kg), ALC+CP and two control groups. Animals were tested on two consecutive days (PND 40-41) in a water maze test assessing spatial learning and memory. While the alcohol-exposed offspring showed deficits on this task, those receiving alcohol + CP performed better than the alcohol-exposed offspring, suggesting that CP-101,606 may be a useful treatment for reducing some damaging effects of fetal alcohol. Although CP appears promising, further investigation is needed to determine its clinical relevance and efficacy in other behavioral deficits.