Moderate prenatal alcohol exposure enhances GluN2B containing NMDA receptor binding and ifenprodil sensitivity in rat agranular insular cortex.

Clark W Bird, Felicha T Candelaria-Cook, Christy M Magcalas, Suzy Davies, C Fernando Valenzuela, Daniel D Savage, Derek A Hamilton

PloS one 2015

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Prenatal exposure to alcohol affects the expression and function of glutamatergic neurotransmitter receptors in diverse brain regions. The present study was undertaken to fill a current gap in knowledge regarding the regional specificity of ethanol-related alterations in glutamatergic receptors in the frontal cortex. We quantified subregional expression and function of glutamatergic neurotransmitter receptors (AMPARs, NMDARs, GluN2B-containing NMDARs, mGluR1s, and mGluR5s) by radioligand binding in the agranular insular cortex (AID), lateral orbital area (LO), prelimbic cortex (PrL) and primary motor cortex (M1) of adult rats exposed to moderate levels of ethanol during prenatal development. Increased expression of GluN2B-containing NMDARs was observed in AID of ethanol-exposed rats compared to modest reductions in other regions. We subsequently performed slice electrophysiology measurements in a whole-cell patch-clamp preparation to quantify the sensitivity of evoked NMDAR-mediated excitatory postsynaptic currents (EPSCs) in layer II/III pyramidal neurons of AID to the GluN2B negative allosteric modulator ifenprodil. Consistent with increased GluN2B expression, ifenprodil caused a greater reduction in NMDAR-mediated EPSCs from prenatal alcohol-exposed rats than saccharin-exposed control animals. No alterations in AMPAR-mediated EPSCs or the ratio of AMPARs/NMDARs were observed. Together, these data indicate that moderate prenatal alcohol exposure has a significant and lasting impact on GluN2B-containing receptors in AID, which could help to explain ethanol-related alterations in learning and behaviors that depend on this region.

Citation

Clark W Bird, Felicha T Candelaria-Cook, Christy M Magcalas, Suzy Davies, C Fernando Valenzuela, Daniel D Savage, Derek A Hamilton. Moderate prenatal alcohol exposure enhances GluN2B containing NMDA receptor binding and ifenprodil sensitivity in rat agranular insular cortex. PloS one. 2015;10(3):e0118721