Brain regional specificity and time-course of changes in the NMDA receptor-ionophore complex during ethanol withdrawal

Gulya, Károly; Grant, Kathleen A.; Valverius, Peter; Hoffman, Paula L.; Tabakoff, Boris

doi:10.1016/0006-8993(91)90583-h

Cited by 158 publications

(112 citation statements)

References 18 publications

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“…These concentrations are similar to those reported in other chronic studies [18,19]. Chronic as well as acute ethanol treatment caused a marked reduction in plasma GSH concentration as well as free and/or proteinbound thiol content.…”

Section: Resultssupporting

confidence: 90%

Nuclear DNA strand breaks during ethanol‐induced oxidative stress in rat brain

et al. 1996

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Free radical-mediated oxidative damage has been implicated in the pathophysiological mechanisms of apoptosis. In this study we report that statistically significant strand breaks were induced primarily in the hippocampus and cerebellum during chronic, and not acute, ethanol treatment. Damage to DNA observed in hippocampus and cerebellum was also correlated with significant modification in the activities of mitochondrial respiratory complexes I and IV and with a significant increase in lipid peroxidation products. This finding lends support to the fact that hippocampus and cerebellum are brain areas particularly vulnerable to redox changes induced by alcohol intoxication, suggesting lower threshold levels of ethanol tolerance.

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Section: Resultssupporting

confidence: 90%

Nuclear DNA strand breaks during ethanol‐induced oxidative stress in rat brain

et al. 1996

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“…It has been demonstrated that NR2A-and NR2B-containing NMDARs are the most sensitive to ethanol (Allgaier, 2002;Lovinger, 1995;Masood et al, 1994;Mirshahi and Woodward, 1995). Although the molecular mechanisms remain to be elucidated, there is a broad consensus that acute ethanol inhibits NMDARs (Calton et al, 1998;Criswell et al, 2003;Hoffman et al, 1989;Kumari and Ticku, 2000;Loftis and Janowsky, 2003;Lovinger et al, 1989;Nie et al, 1994;Martin et al, 1995;Tabakoff and Hoffman, 1996;Tsai and Coyle, 1998;Woodward, 1999;Roberto et al, 2004b), whereas chronic ethanol treatment (CET) leads to a compensatory upregulation of these receptors resulting in increased NMDARmediated function after removal of ethanol (Gulya et al, 1991;Nagy et al, 2004). This increase in NMDARs, and especially the NR2B subunit, may contribute to the ethanol withdrawal syndrome (Kumari and Ticku, 2000;Nagy et al, 2004;Narita et al, 2000;Ripley and Little, 1995;Thomas et al, 1998) that is characterized by both behavioral and electrophysiological parameters (Macey et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Chronic Ethanol Exposure and Protracted Abstinence Alter NMDA Receptors in Central Amygdala

Roberto

Bajo

Crawford

et al. 2005

Neuropsychopharmacol

107

115

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We recently reported that chronic ethanol treatment (CET) and early withdrawal (2-8 h) altered glutamatergic transmission at both preand postsynaptic sites in central nucleus of the amygdala (CeA). Acute ethanol (44 mM) inhibited the NMDA receptor (NMDAR)-mediated EPSCs (NMDA-EPSCs) more in CeA neurons from CET rats than from naïve rats and also decreased paired-pulse facilitation (PPF) of NMDA-EPSCs only in CET rats. To determine whether these CET effects persisted after prolonged withdrawal, we recorded intracellularly in rat CeA slices and measured mRNA and protein expression of CeA NMDAR subunits from CET rats and those withdrawn from ethanol for 1 or 2 weeks. At 1 week withdrawal, acute ethanol decreased evoked NMDA-EPSC amplitudes and NMDA currents induced by exogenous NMDA (B20%) equally to that in naïve rats, indicating that CET effects on postsynaptic mechanisms reversed 1 week after CET cessation. However, acute ethanol still decreased PPF of NMDA-EPSCs, indicating that the acute ethanolinduced increase in glutamate release in CeA seen in CET rats was still present at this time. CET also significantly increased mRNA levels of NR1 and NR2B NMDAR subunits compared to control rats. At 1 week withdrawal, mRNA levels for NR1 and NR2B subunits were significantly decreased. These changes reversed at 2 weeks withdrawal. In Western blots, a significant increase in protein for all three subunits occurred in CeA from CET rats, but not after 1 and 2 weeks of withdrawal. These data indicate that CET induces reversible neuroadaptations in synaptic function, gene expression, and protein composition of NMDAR at CeA synapses. Neuropsychopharmacology (2006) 31, 988-996.

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“…Experimental evidence indicates that prolonged alcohol exposure decreases the sensitivity of GABA receptors (47) and increases the sensitivity of glutamate receptors (24). With the cessation of alcohol intake, these changes are manifested throughout the brain as a decrease in the overall activity of the inhibitory neurotransmitter GABA and an increase in the activity of the excitatory amino acid neurotransmitter glutamate.…”

Section: Neuropharmacology Of Drugs Of Abuse | 29mentioning

confidence: 99%

“…For example, withdrawal seizure-prone mice display a higher incidence of convulsions than do seizureresistant mice when exposed to identical alcohol concentrations (29). Other studies suggest that this alcohol withdrawal reaction is mediated by an increased sensitivity of channels for calcium ions, coupled to receptors for excitatory amino acids (46,47). Several results have emerged in studies of these mouse lines that are potentially important for understanding drug abuse.…”

Section: Alcoholmentioning

confidence: 99%

Biological Components of Substance Abuse and Addiction

1993

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Brain regional specificity and time-course of changes in the NMDA receptor-ionophore complex during ethanol withdrawal

Cited by 158 publications

References 18 publications

Nuclear DNA strand breaks during ethanol‐induced oxidative stress in rat brain

Nuclear DNA strand breaks during ethanol‐induced oxidative stress in rat brain

Chronic Ethanol Exposure and Protracted Abstinence Alter NMDA Receptors in Central Amygdala

Biological Components of Substance Abuse and Addiction

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