NMDA antagonist inhibits rapid tolerance to ethanol

Jm, Khanna; Ph, Wu; Weiner, Jeff L.; Kalant, H.

doi:10.1016/0361-9230(91)90109-w

Cited by 58 publications

(19 citation statements)

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“…In our studies, NMDAR activation appears to play a critical role in the development of acute ethanol tolerance (Khanna et al, 1991), but not in the expression of the tolerance. That is, APV administered during stepwise increases in ethanol prevented LTP even when APV was removed prior to HFS.…”

Section: Discussioncontrasting

confidence: 51%

“…This ischemic tolerance requires NMDAR activation during preconditioning (Kato et al, 1992;Grabb and Choi, 1999). Similarly, tolerance following chronic exposure to opioids can be reversed by ketamine, an NMDAR antagonist (Wong et al, 1996), suggesting that NMDARs play a key role in the expression of this form of tolerance.In our studies, NMDAR activation appears to play a critical role in the development of acute ethanol tolerance (Khanna et al, 1991), but not in the expression of the tolerance. That is, APV administered during stepwise increases in ethanol prevented LTP even when APV was removed prior to HFS.…”

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confidence: 51%

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Modulation of hippocampal long-term potentiation by slow increases in ethanol concentration

2007

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To determine how acute ethanol intoxication may alter memory processing, we examined the effects of stepwise increases in ethanol on long-term potentiation (LTP) in hippocampal slices. LTP was inhibited by acute administration of 60 mM ethanol, but was readily induced if ethanol was increased gradually to 60 mM over 75 min. Administration of 2-amino-5 phosphonovalerate (APV), an Nmethyl-D-aspartate receptor antagonist, during the stepwise increase in ethanol inhibited LTP, suggesting involvement of NMDA receptors in the development of tolerance. However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol. Ethanol-tolerant LTP was inhibited by thapsigargin, suggesting a major role for intracellular calcium release in this form of plasticity. The unique properties of ethanol-tolerant LTP suggest that memories formed during binge drinking are not acquired by standard synaptic mechanisms and that acute tolerance may involve the induction of novel mechanisms to maintain function. KeywordsAlcohol (ethanol); tolerance ; desensitization; allostasis Acute alcohol intoxication is a significant public health problem. During the intoxicated state, problems with motor coordination and cognitive processing are common. Some individuals exhibit profound deficits in memory that may include a complete inability to learn new information, a condition referred to as a 'blackout' (White, 2003). Cognitive and behavioral manifestations associated with acute intoxication are often determined by how ethanol is consumed. Thus, it is possible that both the rate of alcohol consumption and the amount of ethanol consumed are key factors in determining overall effects on the CNS.In hippocampal slices, numerous studies have shown that ethanol inhibits long-term potentiation (LTP), a cellular model of memory and learning (Sinclair and Lo, 1986;Morrisett and Swartzwelder, 1993;Schummers and Browning, 2001). The concentration of ethanol required for LTP inhibition, however, has varied widely among reports. While many studies have found that ethanol inhibits LTP induction at concentrations of 50 mM or more (Randall et al., 1995;Sugiura et al., 1995;Schummers et al., 1997), some reports have shown that concentrations as low as 5 mM also impair LTP induction (Blitzer et al., 1990). The inconsistencies in these studies may reflect experimental differences including slice Correspondence: Yukitoshi Izumi, M.D., Ph.D., Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Box 8134, St. Louis, MO 63110, USA, Phone: +1 314 362 8659, Fax: +1 314 747 2983, Email: izumiy@psychiatry.wustl.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note tha...

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Section: Discussioncontrasting

confidence: 51%

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confidence: 51%

Modulation of hippocampal long-term potentiation by slow increases in ethanol concentration

2007

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“…NMDA antagonists affect both the acquisition and expression of these features. MK-801 and ketmaine block rapid tolerance to ethanol and cross tolerance between ethanol and chlorodiazepoxide [36,56,57,63,88]. Calcium channel antagonists also prevent the development of tolerance to ethanol [24].…”

Section: Behavioral Studiesmentioning

confidence: 99%

Glutamatergic Neurotransmission in Alcoholism

Tsai¹

1998

J Biomed Sci

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Substance abuse and dependence is the most common psychiatric problem. Alcohol is the most commonly abused substance and most people who abuse other substance(s) abuse alcohol at the same time. Accumulating evidence suggests that neurophysiological and pathological effects of ethanol are mediated to a considerable extent via the glutamatergic system. Ethanol disrupts glutamatergic neurotransmission by inhibiting the response of the N-methyl-D-aspartate (NMDA) receptor and by promoting neuronal toxicity through upregulation of the NMDA receptor density. Therefore, short-term/acute ethanol treatment results in a blockade of NMDA receptor-mediated neurotransmission and apoptotic cell death by inhibiting the trophic effect mediated by the NMDA receptor whereas chronic ethanol treatment and withdrawal results in an enhanced toxic response toward glutamate. The neurobiology of human alcoholism such as ethanol intoxication, dependence, withdrawal seizures, delirium tremens, Wernicke-Korsakoff syndrome, and fetal alcohol syndrome can be better understood as a spectrum of consequences of ethanol’s effect on the NMDA glutamatergic system.

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“…One of the Ca2~-permeantion channels in neuronal plasma membranes is the NMDA receptor (NMDAR), and this has been the focus of many studies related to the inhibitory effects of ethanol on receptor function (e.g., Dildy and Leslie, 1989;Gothert and Fink, 1989;Hoffman et al, 1989;Lima-Landman and Albuquerque, 1989;Lovinger et al, 1989; Morrisett et al, 1990;Rabe and Tabakoff, 1990;Woodward and Gonzales, 1990;Khanna et al, 1991;Simson et al, 1991;brio et al, 1992;Snell et al, 1993;Wu et al, 1993; Chandler et aI., 1994;Nie et al, 1994 (Johnston and Morris, 1995), phospholipase A 2 (Dumuis et al, 1988;Lerea and McNamara, 1993), and calcineurin (Halpain et al, 1990).…”

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Effects of Chronic Ethanol Treatment on the Expression of Calcium Transport Carriers and NMDA/Glutamate Receptor Proteins in Brain Synaptic Membranes

Chen

Michaelis

1997

Journal of Neurochemistry

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Acute exposure to ethanol inhibits both the NMDA receptors and the Na/Ca-exchange carriers in neuronal membranes. This alters intraneuronal signaling pathways activated by Ca 2~.Neurons exposed chronically to ethanol exhibit enhanced density and activity of NMDA receptors and increased maximal activity of the exchangers. In the present study, the expression of brain synaptic membrane proteins with ligand binding sites characteristic of NMDA receptors and of exchange carriers were determined after chronic ethanol administration (15 days) to rats. Such treatment caused an increase in the expression of the NMDAR1 receptor subunit, 15% above the levels in the pair-fed controls, as well as of three subunits of a complex that has properties characteristic of NMDA receptors, the glutamate, carboxypiperazinylphosphonate, and glycine binding proteins. Increases for the three binding proteins were 49, 50, and 62%, respectively. The expression of the 1 20-kDa exchanger proteins was increased by 14% and that of a 36-kDa exchanger-associated protein by 33%. Both the binding proteins and the exchangers returned to basal levels within 36-72 h after withdrawal from ethanol. No changes were detected in synaptic membrane Ca2~, Mg2~-ATPases.The enhanced expression of receptor and exchanger-associated proteins may explain the increases in the density and activity of NMDA receptors and exchange carriers after chronic ethanol treatment. Key Words: NMDA receptors-Receptor subunits-Na/ Ca-exchange carriers. J. Neurochem. 69, 1559-1569 (1997).The importance of changes in the concentration of free intracellular calcium (~Ca2~1 1) for normal synaptic transmission as well as for events that lead to prolonged changes in neuronal excitability, such as longterm potentiation (LTP), neuronal development, and neuronal survival, is well documented (e.g., Choi, 1987;Mattson et al., 1988;Ito, 1989;Madison et al., 1991;Ghosh and Greenberg, 1995). Stimuli that disrupt the regulation of intraneuronal Ca 2~may have profound effects on neurotransmission, synaptic plasticity, such as the establishment of LTP and memory formation, synaptogenesis, and neuronal survival. Acute exposure of neurons to ethanol disrupts both the signaling events that are dependent on the transient elevations of intraneuronal Ca2~concentrations and some of the transport processes involved in the maintenance of low intracellular concentrations of this cation (e.g., Harris and Hood, 1980;Messing et al., 1986;Rabe and Weight, 1988;Tabakoff and Hoffman, 1991;Dildy-Mayfield and Leslie, 1991;Carlen et al., 1993).Two main pathways for transient changes in free Ca2~],that are most important in cell signaling are the plasma membrane Ca2-permeant channels and the Ca2-releasing channels in the membranes of intracellular organelles, such as the endoplasmic reticulum. One of the Ca2~-permeantion channels in neuronal plasma membranes is the NMDA receptor (NMDAR), and this has been the focus of many studies related to the inhibitory effects of ethanol on receptor function (e.g., Dild...

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NMDA antagonist inhibits rapid tolerance to ethanol

Cited by 58 publications

References 9 publications

Modulation of hippocampal long-term potentiation by slow increases in ethanol concentration

Modulation of hippocampal long-term potentiation by slow increases in ethanol concentration

Glutamatergic Neurotransmission in Alcoholism

Effects of Chronic Ethanol Treatment on the Expression of Calcium Transport Carriers and NMDA/Glutamate Receptor Proteins in Brain Synaptic Membranes

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