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Long-term intake of ethanol produces adaptive alterations in multiple transmitter systems in the hippocampal formation that likely contribute to ethanol withdrawal-induced seizure and excitotoxicity. The present studies were designed to examine the role of N-methyl-d-aspartate receptor activation and cytosolic Ca(2+) accumulation in the neurotoxic effects(More)
BACKGROUND We recently reported that the sodium salt of acamprosate (Na-acamprosate) demonstrates the characteristics of an antagonist at metabotropic glutamate type 5 receptors (mGluR5s) rather than at N-methyl-d-aspartate receptors (NMDARs). Because mGluR5s are able to enhance the function of NMDARs, this interplay may be involved in the dysregulation of(More)
BACKGROUND Previous studies have shown that withdrawal from ethanol (EtOH) exposure induces neuronal damage, as indicated by propidium iodide (PI) uptake, in organotypic hippocampal slice cultures. This is prevented by MK801, suggesting that damage is "excitotoxic," resulting from activation of N-methyl-d-aspartate (NMDA) receptors by endogenous glutamate.(More)
BACKGROUND Several reported effects of acamprosate within the glutamatergic system could result from interactions with metabotropic glutamate receptors (mGluRs). The following experiments were performed to determine whether acamprosate could compete with trnas-ACPD (+/--1-aminocyclopentane-trans-1,3-dicarboxylic acid, an equimolecular mixture of 1S, 3R and(More)
BACKGROUND It has been suggested that the antirelapse drug acamprosate can inhibit or potentiate glutamate/NMDA receptor-mediated responses via a polyamine site. Additionally, subchronic exposure to acamprosate increases expression of some NMDA receptor subunits. These effects on NMDA receptors imply that the drug may have neurotoxic or neuroprotective(More)
BACKGROUND The antirelapse drug acamprosate has previously been reported to inhibit activating effects of polyamines on -methyl-D-aspartic acid receptor (NMDAR) function. Because increased synthesis of polyamines has been suggested as a mechanism for potentiation of NMDAR function during ethanol withdrawal, we evaluated the effects of acamprosate, MK-801,(More)
Long-term ethanol exposure produces multiple neuroadaptations that likely contribute to dysregulation of Ca(2+) balance and neurotoxicity during ethanol withdrawal. Conversely, nicotine exposure may reduce the neurotoxic consequences of Ca(2+) dysregulation, putatively through up-regulation of the Ca(2+)-buffering protein calbindin-D(28k). The current(More)
BACKGROUND Long-term ethanol dependence results in neuronal adaptation that likely contributes to ethanol withdrawal-induced central nervous system excitability and, potentially, neurotoxicity. This has been suggested to result, in part, from increased release of or response to endogenous polyamines. Furthermore, it has been reported that neurological(More)
BACKGROUND Several reports demonstrate that withdrawal from long-term ethanol exposure is associated with significant central nervous system neurotoxicity, produced at least in part by increased activity of N-methyl-d-aspartate receptors (NMDARs). Recent evidence suggests that elevations in the synthesis and release of the polyamines spermidine and(More)
Heat shock protein (HSP) 72 is released by cells during stress and injury. HSP-72 also stimulates the release of cytokines in macrophages by binding to Toll-like receptors (TLR) 2 and 4. Circulating levels of HSP-72 increase during hepatic ischemia-reperfusion injury. The role of extracellular HSP-72 (eHSP-72) in the injury response to ischemia-reperfusion(More)