FETAL ALCOHOL EXPOSURE ALTERS THE INDUCTION OF IMMEDIATE-EARLY GENE MESSENGER-RNA IN THE RAT PREFRONTAL CORTEX AFTER AN ALTERNATION TASK

The present study examined fetal alcohol effects (FAE) on the inductio n of the immediate early genes (IEGs) c-fos, jun B, c-jun, and zif268 mRNAs in the prefrontal cortex, hippocampus, and other brain regions a fter testing in an alternation task. Subjects were female offspring of Sprague-Dawley rats fed either a 35% ethanol-derived calorie diet, pa ir-fed with sucrose, or control-fed with laboratory chow during the la st week of gestation. At 75-85 days of age, rats were food-deprived an d trained in a t-maze for food reward. Then rats were tested at B-sec, 30-sec, or 60-sec delays on each of 6 days. On the day of killing, a subset of rats was tested at the 60-sec delay for 12 trials and killed 30 min after testing. The remaining animals were killed from their ho me cage and acted as controls. Expression of the four IEG mRNAs was ex amined in the brains of these animals using in situ hybridization. FAE rats showed a memory deficit at the 60-sec delay (p < 0.05), but not at the 0-sec or 30-sec delays. Testing in the alternation task induced a significant elevation of c-fos, c-jun, jun B, and zif268 mRNA expre ssion in the prefrontal cortex, hippocampal subfields CA1 and CA3, and several cortical areas. However, FAE rats showed a significantly smal ler elevation of both c-fos and jun B mRNA levels in the orbital, prel imbic, and anterior cingulate regions of the prefrontal cortex(p < 0.0 5). FAE animals also showed a lower expression of jun B mRNA in the ca udate nucleus. Significant correlations between the mean performance a t the 60-sec delay and mRNA expression of c-fos, jun B, and zif268 in the prefrontal cortical regions (p < 0.05) were observed. These findin gs suggest that fetal alcohol exposure produces changes in the adult p refrontal cortex that may contribute to the behavioral deficit in the alternation task.