Early Postnatal Ethanol Exposure: Glutamatergic Excitotoxic Cell Death During Acute Withdrawal

Using a rat model of binge drinking during the third trimester of pregnancy, we investigated neural markers of glutamatergic activity and cell death during the acute post-ethanol withdrawal period in rats. Ethanol-exposed animals demonstrated increases in markers for glutamatergic activity (NMDA receptors 1 and c-Fos immunoreactivity) and apoptotic cell death (caspase-3 immunoreactivity and cells having fragmented or condensed nuclei identified by Hoechst 33342 staining) in the CA1 and CA3 subfields and dentate gyrus of the hippocampus. Ethanol exposure also increased markers for glutamatergic activity and apoptotic cell death in the prefrontal cortex, dorsal striatum, somatosensory cortex, and motor cortex. The facts that markers for glutamatergic activity and cell death were both elevated in the areas examined, and the magnitudes of the elevation in the two sets of markers correlated negatively, are consistent with a causal link between the two. The results support the hypothesis that NMDA-mediated excitotoxic cell death is involved in neuropathological events that follow ethanol exposures.