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Article Dans Une Revue Addiction Biology Année : 2021

Sex difference in the vulnerability to hippocampus plasticity impairment after binge-like ethanol exposure in adolescent rat: Is estrogen the key?

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Résumé

Binge drinking during adolescence induces memory impairments, and evidences suggest that females are more vulnerable than males. However, the reason for such a difference is unclear, whereas preclinical studies addressing this question are lacking. Here we tested the hypothesis that endogenous estrogen level (E2) may explain sex differences in the effects of ethanol on hippocampus plasticity, the cellular mechanism of memory. Long-term depression (LTD) in hippocampus slice of pubertal female rats was recorded 24 h after two ethanol binges (3 g/kg, i.p., 9 h apart). Neither the estrous cycle nor ethanol altered LTD. However, if ethanol was administered during proestrus (i.e., at endogenous E2 peak), LTD was abolished 24 h later, whereas NMDA-fEPSPs response to a GluN2B antagonist increased. The abolition of LTD was not observed in adult female rats. Exogenous E2 combined with ethanol replicated LTD abolition in pubertal, prepubertal female, and in pubertal male rats without changes in ethanol metabolism. In male rats, a higher dose of ethanol was required to abolish LTD at 24-h delay. In pubertal female rats, tamoxifen, an antagonist of estrogen receptors, blocked the impairing effects of endogenous and exogenous E2 on LTD, suggesting estrogen interacts with ethanol through changes in gene expression. In addition, tamoxifen prevented LTD abolition at 24 h but not at 48-h delay. In conclusion, estrogen may explain the increased vulnerability to ethanol-induced plasticity impairment seen in females compared with males. This increased vulnerability of female rats is likely due to changes in the GluN2B subunit that represent a common target between ethanol and estrogen.
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hal-03584905 , version 1 (22-02-2022)

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Kevin Rabiant, Johan Antol, Mickaël Naassïla, Olivier Pierrefiche. Sex difference in the vulnerability to hippocampus plasticity impairment after binge-like ethanol exposure in adolescent rat: Is estrogen the key?. Addiction Biology, 2021, 26 (4), ⟨10.1111/adb.13002⟩. ⟨hal-03584905⟩

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