Prenatal ethanol exposure, generalized learning impairment, and medial prefrontal cortical deficits in rats

Prenatal ethanol exposure may cause neurological damage and subsequent ment al retardation in humans, with learning deficits similar to those following damage to the prefrontal cortex. This study examined cognitive dysfunction and cortical damage after prenatal exposure to ethanol using a chronic adm inistration model. Pregnant Sprague-Dawley rats received one of three diets during gestation: a liquid diet containing 35% ethanol-derived calories (E TOH), an isocaloric liquid diet (ISO), or standard chow (CHOW). Subjects we re obtained from ETOH dams with blood alcohol concentrations (BACs) above 9 0 mg/dl and corresponding ISO and CHOW controls (one male pup/litter; n = 6 pups/group). At approximately 90 days of age, subjects began training on a series of unique auditory discrimination problems using a successive go/no -go procedure. A criterion of 85% accuracy determined when a rat continued to the next problem. Subjects completed a varying number of problems within a 30-session limit, after which all rats were tested on a tone/click discr imination and reversal. Subjects were then sacrificed and neuronal number i n the medial prefrontal cortex (mPFC) was estimated by the optical fraction ator method. Prenatal ethanol exposure induced significant cell loss in the mPFC, which was associated with significantly impaired reversal learning. Poor performance by ETOH subjects on the tone/click reversal indicates a tr ansfer of training deficit that may reflect failures of inhibitory control. (C) 2001 Elsevier Science Inc. All rights reserved.