NMDA receptor subunit expression after combined prenatal and postnatal exposure to ethanol

Background: The N-methyl-D-aspartate receptor (NMDAR), a subtype of glutamate receptor, is essential for normal neurodevelopment. The brain growth spurt, which is both prenatal and postnatal in the rat, is a time when the brain is especially sensitive to the effects of a teratogen, such as alcohol. Changes in NMDAR function after early perinatal exposure to ethanol (EtOH) may be related to alterations in the expression of secondary subunits. Thus, we investigated the expression of the NR1, NR2A, and NR2B subunits after combined prenatal and postnatal exposure to EtOH. Methods: A binge model was used to administer EtOH (5 g/kg) or isocaloric vehicle to pregnant female rats followed by EtOH (6.2 g/kg) or isocaloric control diet from postnatal days 4 through 9 via an artificial rearing method. Proteins from crude membrane homogenates isolated from cortex and hippocampus at postnatal day 10, 14, or 21 were separated in a standard Western blot procedure. Results: The expression of the NR2A subunit of EtOH-exposed pups showed a significant increase at postnatal day 10 in hippocampus compared with diet controls. No significant changes were seen for any other subunit in either region. Conclusions: The up-regulation of NR2A during EtOH withdrawal is consistent with compensatory changes to prolonged inhibition of the NMDAR. These results indicate that postnatal exposure to ethanol produces distinct effects on the NMDAR, which may underlie deficits associated with alcohol-related neurodevelopmental disorder.