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N-Methyl-D-aspartate (NMDA) receptors (NRs) are ionotropic receptors activated by glutamate and the co-agonist glycine. Ethanol inhibits NMDA receptor function, although its site of action is undefined. We hypothesized that ethanol acts at specific amino acids contained within the transmembrane (TM) domains of the receptor. In this study, NR1 and NR2A(More)
OBJECTIVE Current neuromonitoring techniques in severe human head injury often fail to detect the causes of clinical deterioration. A sensor is now available for continuous monitoring of brain oxygen tension, carbon dioxide tension, and pH values. In this study, brain tissue oxygen tension was used to differentiate patients at risk for brain ischemia and to(More)
The development of ethanol tolerance and dependence reflects neuroadaptive changes in response to continuous depression in synaptic activity. The present study used confocal imaging and electrophysiology procedures to assess the effects of prolonged ethanol exposure on NMDA receptor trafficking in cultures of hippocampal neurons. Neurons exposed to 50 mm(More)
Interferon-alpha (IFNalpha) is a pleomorphic cytokine produced by nucleated cells in response to viral infection. In patients, treatment with IFNalpha has side effects including cognitive impairment resembling subcortical dementia, which is a hallmark of human immunodeficiency virus (HIV)-associated dementia (HAD). IFNalpha is increased in the CSF of HAD(More)
The effects of selected local anesthetics on in vitro and in vivo measurements of dopamine transporter activity were determined to investigate the role of local anesthetic activity in the neuronal actions of cocaine. Cocaine inhibited [3H]2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1.5-naphthalenedisulfonate (CFT) binding and [3H]dopamine uptake with(More)
Estrogen-mediated neuroprotection is observed in neurodegenerative disease and neurotrauma models; however, determining a mechanism for these effects has been difficult. We propose that estrogen may limit cell death in the nervous system tissue by inhibiting increases in intracellular free Ca(2+). Here, we present data using VSC 4.1 cell line, a ventral(More)
N-Methyl-D-aspartate (NMDA) receptors are important targets for drugs of abuse such as ethanol, toluene, and ketamine. Ligand-gated ion channels assembled from the NR1 and NR3 subunits have functional and pharmacological properties that are distinct from those of conventional NMDA receptors containing NR2 subunits. In the present study we used voltage-clamp(More)
Trauma-induced damage to the orbitofrontal cortex (OFC) often results in behavioral inflexibility and impaired judgment. Human alcoholics exhibit similar cognitive deficits suggesting that OFC neurons are susceptible to alcohol-induced dysfunction. A previous study from this laboratory examined OFC mediated cognitive behaviors in mice and showed that(More)
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N-methyl-D-aspartate receptors (NMDA) are glutamate-activated ligand-gated ion channels that participate in diverse forms of synaptic plasticity as well as glutamate-dependent excitotoxicity. Inhibition of the NMDA receptor function may underlie some of the behavioral actions associated with acute exposure to ethanol. The sensitivity of NMDA receptors to(More)