PRENATAL ETHANOL EXPOSURE DECREASES GAP-43 PHOSPHORYLATION AND PROTEIN-KINASE-C ACTIVITY IN THE HIPPOCAMPUS OF ADULT-RAT OFFSPRING

Consumption of moderate quantities of ethanol during pregnancy produce s deficits in long-term potentiation in the hippocampal formation of a dult offspring. Protein kinase C (PKC)-mediated phosphorylation of the presynaptic protein GAP-43 is critical for the induction of long-term potentiation. We tested the hypothesis that this system is affected i n fetal alcohol-exposed (FAE) rats by measuring GAP-43 phosphorylation and PKC activity in the hippocampus of adult offspring of rat dams th at had consumed one of three diets throughout gestation: (a) a 5% etha nol liquid diet, which produced a maternal blood ethanol concentration of 83 mg/dl (FAE); (b) an isocalorically equivalent 0% ethanol diet ( pair-fed); or (c) lab chow ad libitum. Western blot analysis using spe cific anti bodies to PKC-phosphorylated GAP-43 revealed that FAE rats had an similar to 50% reduction in the proportion of phosphorylated GA P-43. Similarly, we found that PKC-mediated incorporation of P-32 into GAP-43 was reduced by 85% in hippocampal slices from FAE rats compare d with both control groups. FAE animals also showed a 50% reduction in total hippocampal PKC activity, whereas the levels of six major PKC i sozymes did not change in any of the diet groups. These results sugges t that GAP-43 phosphorylation deficits in rats prenatally exposed to m oderate levels of ethanol are not due to alterations in the expression of either the enzyme or substrate protein, but rather to a defect in kinase activation.