EFFECTS OF PRENATAL ETHANOL EXPOSURE ON PHOSPHOLIPASE C-BETA-1 AND PHOSPHOLIPASE A(2) IN HIPPOCAMPUS AND MEDIAL FRONTAL-CORTEX OF ADULT-RATOFFSPRING

Previous studies in our laboratory using a rat model of fetal alcohol exposure (FAE) suggest that FAE-induced behavioral deficits are, in pa rt, linked to neurochemical and electrophysiological deficits in long- term potentiation (LTP) in the entorhinal cortical perforant path proj ection to the hippocampal formation. Several findings suggest that sig nal-activated phospholipase C (PLC) and phospholipase A(2) (PLA(2)) ar e critical to the induction and maintenance of LTP. Thus, alterations in phospholipid metabolism may play a significant role in the LTP defi cits observed in FAE offspring. To test this hypothesis, we measured P LC-beta 1 and PLA(2) activities in the hippocampus and medial frontal cortex of adult rats prenatally exposed to ethanol. PLC-beta 1 activit ies were significantly decreased by 20 to 30% in both the hippocampus and medial frontal cortex of FAE rats, compared with ad libitum and pa ir-fed controls. Total Ca2+-dependent PLA(2) activity was 25% lower in the medial frontal cortex of FAE rats, but did not significantly diff er from controls in the hippocampal formation. Approximately 30% of th e measured activity in both the medial frontal cortex and hippocampal formation of ad libitum and pair-fed animals was associated with an 85 kDa cytosolic PLA(2) form. Cytosolic PLA(2) activities were significa ntly reduced in both the medial frontal cortex and hippocampal formati on of FAE rats, compared with controls. These changes in Ca2+-dependen t PLA(2) and PLC-beta 1 activities, coupled with reports of FAE-induce d deficits in protein kinase C activity, indicate that prenatal exposu re to moderate quantities of ethanol causes profound and long-lasting deficits in the cellular signaling mechanisms associated with activity -dependent synaptic plasticity and memory formation.