This R03 Small Grant proposal focuses on two understudied and potentially related research areas in animal models of Fetal Alcohol Syndrome (FAS): (a) Effects of prenatal ethanol exposure on generalized learning, such as that resulting from experience with a series of problems that have a common solution strategy (i.e., learning set, or """"""""learning-to-learn""""""""), and (b) morphological effects on the prefrontal cortex. Evidence for a relation between deficits in generalized learning and prefrontal damage comes from lesion studies in otherwise intact animals and animal models of mental retardation. Our pilot data indicate that a behavioral measure of generalized learning in rats is affected by prenatal ethanol exposure. Stereological methods will be used to make accurate measures of cell number in the rat brain. The proposed studies will determine whether there is a correlation between deficits in generalized learning and prefrontal cortical cell number. Results documenting such a correlation would set the stage for further investigations of the effects of prenatal ethanol exposure on developing cortex and subsequent deficits in generalized learning. Additional measures of task-specific (i.e., non-generalized) learning will serve as a contrast and allow us to better relate our findings to existing literature. In a rat model of prenatal ethanol exposure, we will compare data from ethanol-exposed subjects and two non-exposed control groups (isocaloric pair fed and ad lib chow fed) on several dependent measures: (1) Three behavioral measures of non-spatial task-specific learning: free-operant lever pressing, response-independent stimulus-reward associative learning, and acquisition of an auditory discrimination. (2) Three behavioral measures of non-spatial task-general learning: a series of repeated reversals of one discrimination problem, acquisition of a series of different discrimination problems, and transfer of training from one problem type to the other. (3) Cell-number estimates for prefrontal cortex (layers 11 and V) obtained by the optical fractionator stereological method. (4) Within-subject correlations of ethanol exposure, cell number, and learning.
| Mihalick, S M; Crandall, J E; Langlois, J C et al. (2001) Prenatal ethanol exposure, generalized learning impairment, and medial prefrontal cortical deficits in rats. Neurotoxicol Teratol 23:453-62 |
