Ethanol, sedative hypnotics, and glutamate receptor function in brain and cultured cells

  title={Ethanol, sedative hypnotics, and glutamate receptor function in brain and cultured cells},
  author={Boris Tabakoff and Paula L. Hoffman},
  journal={Behavior Genetics},
Ethanol, acutely, is a potent and selective inhibitor of the function of theN-methyl-d-aspartate (NMDA) subtype of glutamate receptor in primary cultures of cerebellar granule cells. The effect of ethanol can be reversed by high concentrations of glycine, and nonequilibrium ligand binding studies in brain membrane preparations suggest that ethanol may act by decreasing the frequency of ion channel opening. After chronic consumption of ethanol by animals, the number of NMDA receptors (measured… 

Regulation of NMDA receptors by ethanol.

  • M. KumariM. Ticku
  • Biology, Medicine
    Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques
  • 2000
Ethanol's effects on NMDA receptors, including alteration in receptor function and number, probably result from interplay of multiple mechanisms some of which are discussed here.

Aberrant Synaptic Activation of N-Methyl-d-aspartate Receptors Underlies Ethanol Withdrawal Hyperexcitability

It is demonstrated that hyperexcitability triggered by withdrawal from chronic ethanol exposure is associated with increases in both synaptic NMDA receptor expression and activation and results from changes in both postsynaptic function as well as presynaptic release.

Role of glutamatergic and GABAergic systems in alcoholism.

  • K. DavisJ. Wu
  • Medicine, Psychology
    Journal of biomedical science
  • 2001
One of the new family of NMDA receptor antagonists, such as DETC-MESO, which regulate the redox site ofNMDA receptors, may prove to be the drug of choice for treating alcoholism as well as many neurological diseases.

Role of Glutamatergic and GABAergic Systems in Alcoholism

Recent progress in glutamatergic and GABAergic systems is reviewed with a special focus on their roles in alcohol dependence and alcohol withdrawal-induced seizures, and a new family of NMDA receptor antagonists such as DETC-MESO may prove to be the drug of choice for treating alcoholism as well as many neurological diseases.

Pharmacological and Anatomical Evidence for an Interaction Between mGluR5- and GABAA α1-Containing Receptors in the Discriminative Stimulus Effects of Ethanol

Results indicated that mGluR5- and GABAA α1-containing receptors were both coexpressed in limbic brain regions and colocalized on the same cells in specific brain regions including the amygdala, hippocampus, globus pallidus, and ventral pallidum.

The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice

Analysis of the temporal pattern of responding showed that MPEP reduced ethanol-reinforced responding during peak periods of behavior occurring during the early hours of the dark cycle, indicating that mGlu5 receptors selectively regulate the onset and maintenance of ethanol self-administration in a manner that is consistent with reduction in ethanol’s reinforcement function.

Alcohol Modulation of Dopamine Release

The rationale for this study was predicated on the belief that advancement in the understanding of the brain mechanisms underlying the recreational use and abuse potential of alcohol will pave the way for more effective treatment strategies that could reverse alcohol dependence and co-dependence and save lives and resources throughout the world.



Ethanol withdrawal seizures and the NMDA receptor complex.

Chronic exposure of cerebellar granule cells to ethanol results in increased N-methyl-D-aspartate receptor function.

The results demonstrate that the response to NMDA is significantly enhanced after chronic in vitro exposure of the cells to ethanol, and suggest that chronic ethanol exposure produces a selective up-regulation of NMDA receptor function in the intact animal.

Ethanol inhibits NMDA-evoked electrophysiological activity in vivo.

Evidence is provided that ethanol, when administered by the systemic route to rats, also inhibits NMDA-evoked electrophysiological activity in vivo at behaviorally relevant doses, and it is indicated that additional neural actions must contribute to ethanol's pharmacological profile.

Ethanol inhibits NMDA-activated ion current in hippocampal neurons.

The potency for inhibition of the NMDA-activated current by several alcohols is linearly related to their intoxicating potency, suggesting that alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication.

Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-D-aspartate receptor.

The results demonstrate that the in vivo actions of ethanol on the NMDA systems of brain may be dependent on glycine concentrations at these receptor sites.

Prolonged ethanol inhalation decreases gamma-aminobutyric acidA receptor alpha subunit mRNAs in the rat cerebral cortex.

Ethanol administration to rats by ethanol vapor inhalation results in a 40-50% reduction in the level of gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit mRNAs in the cerebral cortex, which may underlie alterations in GABAA receptor function or number observed following prolonged ethanol exposure in rats.

Cloning of cDNA for the glutamate-binding subunit of an NMDA receptor complex

The isolation and characterization of a protein complex of four major proteins that represents an intact complex of the NMDA receptor ion channel is reported and the cloning of the cDNA for one of the subunits of this receptor complex, the glutamate-binding protein is reported on.

Are changes in neuronal calcium channels involved in ethanol tolerance?

  • S. DolinH. Little
  • Medicine, Biology
    The Journal of pharmacology and experimental therapeutics
  • 1989
The results suggest that alterations in dihydropyridine-sensitive calcium channels may be involved in the adaptations that occur on chronic treatment with ethanol, as well as the general anesthetic effects of ethanol in mice.