ALCOHOL EXPOSURE DURING BRAIN-DEVELOPMENT REDUCES H-3 MK-801 BINDING AND ENHANCES METABOTROPIC-GLUTAMATE RECEPTOR-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS IN RAT HIPPOCAMPUS

Glutamate receptors play important roles during brain development. We have investigated the effect of chronic maternal alcohol intake on the ontogenic profile of hippocampal glutamate receptor subtypes in their offspring. Binding of H-3-MK-801 to N-methyl-D-aspartate (NMDA) receptor was measured in isolated membranes from the hippocampus of the offspring of pair-fed control and alcohol-fed rats at different times during the postnatal life. Phosphatidylinositol triphosphate (PIP2) hydrolysis was also assayed to provide a measure of the possible effect of ethanol on the metabotropic glutamate receptor (mGluR). In pair-fed control rats, at postnatal day (PND) 3, the H-3-MK-801 binding represents 60% of adult values. Binding then rises to 170% at PND 11, and gradually decreases to adult levels. A transient overshoot in the mGluR-coupled PIP2 hydrolysis was also observed during postnatal development in rat hippocampus. Alcohol-exposed rats showed a similar pattern, but a significant decrease in the specific binding for NMDA receptor was observed on all the postnatal days analyzed. In addition, alcohol exposure significantly decreases the number of specific H-3-MK-801 binding sites. with no change in the affinity of the sites for H-3-MK-801. Moreover, this treatment mGluR-activated PIP2 hydrolysis enhanced the hippocampus of alcohol-exposed rats. These results may contribute to an understanding of the toxic effects of ethanol on the developing central nervous system (CNS) and help explain the cognitive deficits associated with prenatal alcohol exposure.