ArticleAlcoholism, clinical and experimental research2013
Probing the modulation of acute ethanol intoxication by pharmacological manipulation of the NMDAR glycine co-agonist site.
Article in Alcoholism, clinical and experimental research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Astroglial correlates of neuropsychiatric disease: From astrocytopathy to astrogliosis.Progress in neuro-psychopharmacology & biological psychiatry · 2018Review
- Mouse strain differences in punished ethanol self-administration.Alcohol (Fayetteville, N.Y.) · 2017Article
- Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective.F1000Research · 2017Review
- Acute Ethanol Inhibition of γ Oscillations Is Mediated by Akt and GSK3β.Frontiers in cellular neuroscience · 2016Article
- D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Tolerance to ethanol intoxication after chronic ethanol: role of GluN2A and PSD-95.Addiction biology · 2015Article
- NMDA receptor subunits and associated signaling molecules mediating antidepressant-related effects of NMDA-GluN2B antagonism.Behavioural brain research · 2015Article
- Investigational therapies for the pharmacological treatment of alcoholism.Expert opinion on investigational drugs · 2015Article
- Glutamatergic targets for new alcohol medications.Psychopharmacology · 2013Review
- Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.PloS one · 2013Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundStimulating the glycine(B) binding site on the N-methyl-d-aspartate ionotropic glutamate receptor (NMDAR) has been proposed as a novel mechanism for modulating behavioral effects of ethanol (EtOH) that are mediated via the NMDAR, including acute intoxication. Here, we pharmacologically interrogated this hypothesis in mice.
methodsEffects of systemic injection of the glycine(B) agonist, d-serine, the GlyT-1 glycine transporter inhibitor, ALX-5407, and the glycine(B) antagonist, L-701,324, were tested for the effects on EtOH-induced ataxia, hypothermia, and loss of righting reflex (LORR) duration in C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mice. Effects of the glycine(B) partial agonist, d-cycloserine (DCS), the GlyT-1 inhibitor, N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), and the glycine(B) antagonist, 5,7-dichlorokynurenic (DCKA), on EtOH-induced LORR duration were also tested. Interaction effects on EtOH-induced LORR duration were examined via combined treatment with d-serine and ALX-5407, d-serine and MK-801, d-serine and L-701,324, as well as L-701,324 and ALX-5407, in B6 mice, and d-serine in GluN2A and PSD-95 knockout mice. The effect of dietary depletion of magnesium (Mg), an element that interacts with the glycine(B) site, was also tested.
resultsNeither d-serine, DCS, ALX-5407, nor NFPS significantly affected EtOH intoxication on any of the measures or strains studied. L-701,324, but not DCKA, dose-dependently potentiated the ataxia-inducing effects of EtOH and increased EtOH-induced (but not pentobarbital-induced) LORR duration. d-serine did not have interactive effects on EtOH-induced LORR duration when combined with ALX-5407. The EtOH-potentiating effects of L-701,324, but not MK-801, on LORR duration were prevented by d-serine, but not ALX-5407. Mg depletion potentiated LORR duration in B6 mice and was lethal in a large proportion of S1 mice.
conclusionsGlycine(B) site activation failed to produce the hypothesized reduction in EtOH intoxication across a range of measures and genetic strains, but blockade of the glycine(B) site potentiated EtOH intoxication. These data suggest endogenous activity at the glycine(B) opposes EtOH intoxication, but it may be difficult to pharmacologically augment this action, at least in nondependent subjects, perhaps because of physiological saturation of the glycine(B) site.
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