The impact of prenatal alcohol exposure on hippocampal-dependent outcome measures is influenced by prenatal and early-life rearing conditions

The clinical course of individuals exposed to alcohol in utero is influenced by multiple factors, including the social environments of the gravid female and offspring. In the present studies we focused on the effects of prenatal alcohol exposure (PAE) and the prenatal and early-life social environments on the hippocampal formation, as impaired development and functioning of this brain region have been implicated in several of the adverse cognitive outcomes associated with PAE.

These studies demonstrate a complex interplay between the effects of PAE and social environments. The findings have important translational implications, as well as highlight the importance of considering rearing conditions in the interpretation of research findings on PAE.

We combined our PAE mouse model with 2 conditions of housing pregnant dams and their preweanling offspring: the standard nest (SN), in which a dam is individually housed prior to parturition and then remains isolated with her offspring, and the communal nest (CN), in which multiple dams are housed together prior to parturition and then following delivery the moms and their litters share a nest. Mouse dams consumed either 10% (w/v) ethanol in 0.066% (w/v) saccharin (SAC) or 0.066% (w/v) SAC alone using a limited (4-hour) access, drinking-in-the-dark paradigm. Immunoblotting techniques were used to measure levels of the glucocorticoid receptor (GR), 11-β-hydroxysteroid dehydrogenase 1, the FK506-binding proteins 51 and 52, and corticotropin-releasing hormone receptor type 1 in the hippocampal formation isolated from male adolescent offspring. We also determined the effect of PAE and rearing conditions on context discrimination, a hippocampal-dependent learning/memory task.

SN PAE offspring displayed impaired context discrimination and neurochemical changes in the hippocampal formation consistent with increased GR nuclear localization. These effects of PAE were, in general, ameliorated in mice reared in a CN. The CN also altered neurochemical measures and improved learning/memory in SAC control animals. Conclusions: These studies demonstrate a complex interplay between the effects of PAE and social environments. The findings have important translational implications, as well as highlight the importance of considering rearing conditions in the interpretation of research findings on PAE.