The broad long-term objective of this project is to develop a rat model of the persistent mental deficits associated with the human fetal alcohol syndrome (FAS). A well characterized animal model is a prerequisite for experimentally determining critical prenatal exposure periods, the minimal blood alcohol concentration (BAC) required to produce these effects, the specific neuropathology of biomolecular mechanism involved as well as for testing prophylactic or therapeutic regimens.
The specific aim of this project is to evaluate a four level chained response schedule (reinforced with water) as a criterion for detecting, characterizing and quantifying learning deficits induced in rats (male, Sprague Dawley) by prenatal exposure to alcohol. Persistence of behavioral effects will be determined by analyzing the consecutive acquisition of as many different four lever sequences as the subjects will learn over their life-span. The basic data collected are; the number of incorrect responses (ICR) and time to correct responses (CR) per lever, per reinforcement as well as total reinforcements, R's during pre-session hold and during ICR, time-out (T.O.). Treatment differences will be assessed using ANOVA Techniques. Intra- and Inter-session schedule acquisition statistics (learning curves) will be determined by regression analysis of percent CR's and other pertinent data. Five experimental groups of 12 (litter) male rats each will be evaluated and prenatally treated as follows: nontreated control (EGC) as well as four alcohol intubated groups - zero (EGO), 2 (EG2), 4 (EG4) and 8g/kg/day (EG8). Treatments will be administered daily in divided doses (0800 and 1600 hours) from GD-6 to GD-20. Groups EG1, EG2 and EG3 will be pair fed and watered to the EG4 group. BAC's will be determined using a Sigma Diagnostic Kit (#332UV). Blood from the tail vein will be taken for analysis at 1700 hours on GD-11, 14 and 17. At whelping, litters will be culled to 5 male and 5 females each and the pups surrogate fostered. At weaning (21 days) rats to be tested will be caged individually. Subjects will be lever conditioned at about 100 days and behaviorally tested 1 hour a day, 5 days a week thereafter. The rats will be weighed daily from weaning and at autopsy brain weight and head size will be determined.
