University of Kentucky
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
Faculty Advisor/ Mentor
Susan Barron; Ana Hutton Kehrberg
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.
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.