Fetal associative learning mediated through maternal alcohol intoxication

Background: The aim of the present study was to analyze whether alcohol as an unconditioned stimulus is capable of supporting associative learning in near-term fetuses. Methods: In experiment 1, we determined pharmacokinetic profiles of alcohol and of an aromatic substance (cineole) in amniotic fluid and maternal blood during late gestation. The results obtained through gas chromatographic analysis allowed a second experiment in which we explicitly paired peak levels of cineole with peak levels of alcohol in amniotic fluid and blood, by intragastrically administering cineole and ethanol to the dams during gestational days 17 through 20 (paired condition). Control groups were dams given cineole 4 hr before commencement of an acute state of alcohol intoxication (long-delay group) or were only exposed to water administrations (water control group). The progeny were evaluated during postnatal day 16 in terms of behavioral responsiveness to intraorally infused solutions (cineole or alcohol presented in milk vehicle, or milk alone). Results: Mouthing responsiveness to cineole was strongly affected by the nature of prenatal treatments. Pups in the paired prenatal condition mouthed significantly less than did long-delay and water controls. Physical and behavioral measures allowed us to reject the possibility that these effects were due to teratogenic effects of alcohol during late gestation. Conclusions: These results indicate that before birth, rat fetuses are capable of acquiring associative memories supported by the unconditioned properties of alcohol. This associative memory can be expressed during infancy through a significant reduction in mouth movements in the presence of the specific orosensory cue explicitly paired with alcohol interoceptive effects in utero.