Early postnatal ethanol exposure in mice induces sex-dependent memory impairment and reduction of hippocampal NMDA-R2B expression in adulthood

Drinking alcohol during pregnancy is particularly detrimental for the developing brain and may cause a broad spectrum of cognitive and behavioral impairments, collectively known as fetal alcohol spectrum disorders (FASDs). While behavioral abnormalities and brain damage have been widely investigated in animal models of FASD, the sex differences in the vulnerability to perinatal ethanol exposure have received less consideration. Here we investigated the long-term behavioral and molecular effects of acute ethanol-binge like exposure during the early postnatal period (equivalent to the third trimester of human pregnancy) in adult male and female mice. CD1 mice received a single ethanol exposure on P7 and were analyzed starting from P60. We found that ethanol-exposed mice showed increased activity in the open field test and in the plus-maze test, regardless of the sex. Interestingly, only ethanol-exposed adult male mice exhibited memory impairment in the water maze and fear-conditioning tests. Remarkably, hippocampal levels of NMDA-R2B were reduced only in ethanol-exposed male, while total BDNF levels were increased in both male and female ethanol-exposed mice. Our data suggest a different susceptibility of early postnatal ethanol exposure in male and female CD1 mice.