title: Two Binges of Ethanol a Day Keep the Memory Away in Adolescent Rats: Key Role for GLUN2B Subunit.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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).
authors.forename: Benoit
authors.initials: B
authors.lastname: Silvestre de Ferron
authors.affiliation: 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).
authors.forename: Khaled-Ezaheir
authors.initials: KE
authors.lastname: Bennouar
authors.affiliation: 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).
authors.forename: Myriam
authors.initials: M
authors.lastname: Kervern
authors.affiliation: 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).
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Alaux-Cantin
authors.affiliation: 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).
authors.forename: Alexandre
authors.initials: A
authors.lastname: Robert
authors.affiliation: 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).
authors.forename: Kevin
authors.initials: K
authors.lastname: Rabiant
authors.affiliation: 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).
authors.forename: Johann
authors.initials: J
authors.lastname: Antol
authors.affiliation: 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).
authors.forename: Mickaël
authors.initials: M
authors.lastname: Naassila
authors.affiliation: 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.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pierrefiche
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D063425:Binge Drinking / Q000150:complications* / Q000209:etiology; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000097:blood; D004558:Electric Stimulation; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D012694:Serine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D012694:Serine
keywords: NMDA; binge; cognition; ethanol; hippocampus; long-term synaptic depression