Format

Send to

Choose Destination
Int J Neuropsychopharmacol. 2015 Aug 6;19(1). pii: pyv087. doi: 10.1093/ijnp/pyv087.

Two Binges of Ethanol a Day Keep the Memory Away in Adolescent Rats: Key Role for GLUN2B Subunit.

Author information

1
INSERM ERI-24, GRAP, Groupe de Recherche sur l'Alcool et les Pharmacodépendances, Université Picardie Jules Verne, Bât. CURS, CHU-Sud, Amiens, France (Mr Silvestre de Ferron, Bennouar PhD, Kervern PhD, Alaux-Cantin PhD, Mr Robert, Mr Rabiant, Mr Antol, Naassila PhD, and Pierrefiche PhD).
2
INSERM ERI-24, GRAP, Groupe de Recherche sur l'Alcool et les Pharmacodépendances, Université Picardie Jules Verne, Bât. CURS, CHU-Sud, Amiens, France (Mr Silvestre de Ferron, Bennouar PhD, Kervern PhD, Alaux-Cantin PhD, Mr Robert, Mr Rabiant, Mr Antol, Naassila PhD, and Pierrefiche PhD). op-lnc@u-picardie.fr.

Abstract

BACKGROUND:

Binge drinking is common in adolescents, but the impact of only a few binges on learning and memory appears underestimated. Many studies have tested the effects of long and intermittent ethanol exposure on long-term synaptic potentiation, and whether long-term synaptic depression is affected remains unknown.

METHODS:

We studied the effects of one (3 g/kg, i.p.; blood ethanol content of 197.5±19 mg/dL) or 2 alcohol intoxications (given 9 hours apart) on adolescent rat's memory and synaptic plasticity in hippocampus slice after different delay.

RESULTS:

Animals treated with 2 ethanol intoxications 48 hours before training phase in the novel object recognition task failed during test phase. As learning is related to NMDA-dependent mechanisms, we tested ketamine and found the same effect as ethanol, whereas D-serine prevented learning deficit. In hippocampus slice, NMDA-dependent long-term synaptic depression was abolished 48 hours after ethanol or ketamine but prevented after D-serine or in a low-Mg(2+) recording medium. Long-term synaptic depression abolition was not observed 8 days after treatment. An i.p. treatment with MK-801, tetrahydroisoxazolopyridine, or muscimol was ineffective, and long-term synaptic potentiation, intrinsic excitability, and glutamate release remained unaffected. The input/ouput curve for NMDA-fEPSPs was shifted to the left 48 hours after the binges with a stronger contribution of GluN2B subunit, leading to a leftward shift of the Bienenstock-Cooper-Munro relationship. Interestingly, there were no cellular effects after only one ethanol injection.

CONCLUSION:

Two ethanol "binges" in adolescent rats are sufficient to reversibly abolish long-term synaptic depression and to evoke cognitive deficits via a short-lasting, repeated blockade of NMDA receptors only, inducing a change in the receptor subunit composition. Furthermore, ethanol effects developed over a 48-hour period of abstinence, indicating an important role of intermittence during a repeated long-duration binge behavior.

KEYWORDS:

NMDA; binge; cognition; ethanol; hippocampus; long-term synaptic depression

PMID:
26254123
PMCID:
PMC4772273
DOI:
10.1093/ijnp/pyv087
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center