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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-Mg2+ 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.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03589643
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Soumis le : vendredi 25 février 2022 - 17:11:03
Dernière modification le : mercredi 7 septembre 2022 - 10:38:21

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Benoit Silvestre De Ferron, Khaled-Ezaheir Bennouar, Myriam Kervern, Stephanie Alaux-Cantin, Alexandre Robert, et al.. Two Binges of Ethanol a Day Keep the Memory Away in Adolescent Rats: Key Role for GLUN2B Subunit. International Journal of Neuropsychopharmacology, Oxford University Press (OUP), 2016, 19 (1), ⟨10.1093/ijnp/pyv087⟩. ⟨hal-03589643⟩

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