Alcohol administration during critical developmental periods has been associated with a constellation of behavioral, cellular, and physiological abnormalities. While a wide array of alcohol-associated teratogenic effects have been well established, the specific mechanisms through which alcohol produces early developmental impairments are still under investigation. In addition to the numerous main effects of alcohol exposure, it has been hypothesized that an NMDA-mediated excitotoxic reaction associated with alcohol withdrawal also contributes to alcohol's neurotoxic effects. In the present study, a rodent model of fetal alcohol syndrome was employed to assess effects of short-term acute neonatal alcohol exposure, as well as to reveal contributory deficiencies resulting from NMDA-mediated glutamatergic excitotoxicity during the alcohol withdrawal period. Rat pups were administered binge levels of ethanol during postnatal day 6, and then subsequently treated with either saline or MK-801, a potent non-competitive NMDA receptor antagonist, during the ethanol withdrawal stage. Once the subjects reached juvenile age, they were prepared for Pavlovian delay eyeblink conditioning. Eyeblink conditioning provides an ideal model of associative learning with well-delineated brainstem/cerebellar circuitry that allows for precise quantification of ethanol-associated impairments at a number of levels. Results showed that subjects treated with ethanol displayed learning-related deficiencies during eyeblink conditioning tasks, as well as cytological and physiological abnormalities in underlying cerebellar structures. Furthermore, subjects subsequently treated with MK-801 following ethanol exhibited partial protection from ethanol-associated deficits. These results support the role of NMDA-mediated excitotoxicity during ethanol withdrawal as a significant component of the neurotoxic effects of neonatal ethanol exposure. Additionally, these data also suggest that directed NMDA receptor blockade during the withdrawal period successfully attenuates observed deficiencies.My work on this project has been to analyze and explore the range of these effects using the powerful associative ... Chapter 2 will introduce the behavioral methodology of eyeblink conditioning used throughout this thesis; specifically the anbsp;...
|Title||:||Effects of Acute Neonatal Ethanol Exposure and Subsequent MK-801 Administration During Rodent Eyeblink Conditioning|
|Author||:||Brandt W. Young|
|Publisher||:||ProQuest - 2007|