Ethanol sensitivity of NMDA receptors

Allgaier, Clemens

doi:10.1016/s0197-0186(02)00046-3

Cited by 110 publications

(90 citation statements)

References 47 publications

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“…The asterisk denotes statistical significance (po0.05). subunits, the most ethanol-sensitive NMDAR subunits (Allgaier, 2002;Lovinger, 1995;Mirshahi and Woodward, 1995). We found that in CeA neurons from 1 weekwithdrawn rats, acute ethanol decreased both the evoked NMDA-EPSC amplitudes and postsynaptic NMDA currents to the same extent as in naïve rats, suggesting that these CET-induced effects recovered within 1 week of cessation of CET.…”

Section: Discussionmentioning

confidence: 60%

“…A prominent electrophysiological effect of acute ethanol is a decrease in current generated by NMDAR activation (Criswell and Breese, 2005;Criswell et al, 2003;Fadda and Rossetti, 1998;Kalluri et al, 1998;Lovinger, 2002;Lovinger et al, 1989;Nie et al, 1994;Roberto et al, 2004b;Tabakoff and Hoffman, 1996;Tsai and Coyle, 1998;Woodward, 2000;Yang et al, 1996). The sensitivity of NMDAR channels to ethanol is dependent on the NR2 subunit expressed: for example, NMDARs with NR1/2A and NR1/2B subunits are the most sensitive to ethanol (Allgaier, 2002;Lovinger, 1995;Mirshahi and Woodward, 1995). In contrast to mature hippocampus and cortex where NR1/NR2A subunits predominate (Chavis and Westbrook, 2001;Okabe et al, 1998;Scheetz and Constantine-Paton, 1994;Tovar and Westbrook, 1999), in the CeA, the NMDARs are composed mainly of NR1/NR2B subunits and with little or no developmental change in subunit composition (Lopez de Armentia and Sah, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Roberto

Bajo

Crawford

et al. 2005

Neuropsychopharmacol

108

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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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Roberto

Bajo

Crawford

et al. 2005

Neuropsychopharmacol

108

115

View full text Add to dashboard Cite

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“…Adding to this complexity, various subunit combinations can vary widely in their pharmacology (Wafford et al, 1993). A number of studies examining recombinant NMDARs suggest that those containing NR2A or NR2B subunits may display twice the sensitivity to ethanol as those including NR2C or NR2D (Kuner et al, 1993;Masood et al, 1994;Mirshahi & Woodward, 1995; for reviews see Allgaier, 2002;Sucher et al, 1996). NR2B-containing receptors also display the greatest sensitivity to polyamine stimulation, due to their increased number of polyamine binding sites (Williams, 1994;Williams et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…During withdrawal, this up-regulation has been shown to result in glutamatergic hyperexcitability and cell death (Gibson et al, 2003;Hoffman et al, 1995;Iorio et al, 1993). Thomas et al (1997;2002) have shown that administration of an NMDAR antagonist, MK-801, to neonatal pups during ethanol withdrawal reduced some of the deficits associated with prenatal ethanol exposure. The timing of MK-801 treatment, however, appeared critical .…”

Section: Introductionmentioning

confidence: 99%

Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure

Lewis

Wellmann

Barron

2007

Pharmacology Biochemistry and Behavior

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This study examined the effects of binge-like ethanol (ETOH) exposure in neonatal rats on a cerebellar-mediated balance task, and the ability of agmatine, an n-methyl-d-aspartate receptor (NMDAR) modulator, to reverse such effects. Five neonatal treatments groups were used, including ETOH (6.0 g/kg/day), AG (20 mg/kg), ETOH plus AG (6.0 g/kg/day and 20 mg/kg), a maltose control, and a non-treated control. Ethanol was administered via oral intubation twice daily for eight days, (AG was administered with the last ETOH intubation only). Two exposure periods were used; PND 1-8 or PND 8-15. On PND 31-33, balance performance on a single dowel was tested. Treatment with AG during withdrawal in ETOH exposed animals improved performance relative to ETOH alone among the PND 1-8 exposure period. ETOH exposure during the 2 nd postnatal week did not impair balance. These findings provide further support that exposure to ETOH during critical developmental periods can impair performance on a cerebellar-dependent balance task. Of perhaps greater significance, co-administration of agmatine reduced these deficits suggesting that NMDA modulation via polyamine blockade may provide a novel approach to attenuating damage associated with binge-like ETOH consumption.

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GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal

Rujescu

Soyka

Dahmen³

et al. 2005

American J of Med Genetics Pt B

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N-Methyl-D-aspartate (NMDA) receptors, members of the glutamate receptor channel superfamily, are generally inhibited by alcohol. The expression and alternative splicing of the obligatory NR1 subunit is altered by alcohol exposure, emphasizing the involvement of the NR1 subunit, which is coded by the GRIN1 gene, in alcohol-mediated effects. We performed an association study in patients with alcohol dependence with the GRIN1 locus. Two independent case control samples consisting of a total of 442 alcohol-dependent patients and 442 unrelated controls were included. There was no overall difference in allele or genotype frequency between patients and controls. However, the 2108A allele and A-containing genotypes were over-represented in the patients with a history of withdrawal-induced seizures when compared to healthy volunteers (allele: chi(2) = 5.412, df = 1, P = 0.020) or an independent sample of patients without a history of seizures (allele: chi(2) = 4.185, df = 1, P = 0.041). Age at onset, years of alcohol dependence, and a history of delirium tremens did not differ between genotype or allele groups. These findings support the hypothesis that the GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal. This novel finding warrants replication.

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Ethanol sensitivity of NMDA receptors

Cited by 110 publications

References 47 publications

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

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

Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure

GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal

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