Fetal learning about ethanol and later ethanol responsiveness: evidence against "safe" amounts of prenatal exposure

Abstract

Near-term fetuses of different mammalian species, including humans, exhibit functional sensory and learning capabilities. The neurobiological literature indicates that the unborn organism processes sensory stimuli present in the amniotic fluid, retains this information for considerable amounts of time, and is also capable of associating such stimuli with biologically relevant events. This research has stimulated studies aimed at the analysis of fetal and neonatal learning about ethanol, a topic that constitutes the core of the present review. Ethanol has characteristic sensory (olfactory, taste, and trigeminal) attributes and can exert pharmacologic reinforcing effects. The studies under examination support the hypothesis that low to moderate levels of maternal ethanol intoxication during late pregnancy set the opportunity for fetal learning about ethanol. These levels of prenatal ethanol exposure do not generate evident morphologic or neurobehavioral alterations in the offspring, but they exert a significant impact upon later ethanol-seeking and intake behaviors. Supported by preclinical and clinical findings, this review contributes to strengthening the case for the ability of prenatal ethanol exposure to have effects on the postnatal organism.

Figure 1

Mouthing duration (sec) generated by cineole intraoral infusions as a function of prenatal treatment (water group, paired group, and long-delay group) and interval of the test (−2, −1, 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9 mins). Intraoral stimulation took place during interval 0. Vertical lines represent the standard errors of the means (adapted from Ref. 118). The asterisk denotes significant differences between the paired group and the remaining prenatal treatments.

Figure 2

Time of attachment (seconds) to a nutritive surrogate nipple as a function of prenatal treatment (water group, paired group, and long-delay group) and the odor presented at testing (cineole or no odor). The test had a total duration of 10 mins. Vertical lines represent the standard errors of the means (adapted from Ref. 125). The asterisk denotes significant differences between the paired group stimulated with cineole and the remaining treatment conditions.

Figure 3

(A) Mean grasp duration (seconds) elicited by a nutritive surrogate nipple as a function of prenatal treatment (water group, paired group, and long-delay group) when newborns were exposed to cineole odor before the test situation. Mean grasp durations correspond to the first and second half of the test (1–8 and 9–15 mins, respectively) (adapted from Ref. 125). (B) Mean grasp duration (seconds) to a nutritive surrogate nipple as a function of prenatal treatment (water group, paired group, and long-delay group). Neonates were pretreated with intragastric administrations of ethanol or water before being tested. Vertical lines represent the standard errors of the means. Asterisks denote significant differences between the paired group and the remaining prenatal treatments (A) and the significant difference existing between paired animals treated with ethanol before the test and the remaining control conditions (B).

Figure 4

Time of attachment to a surrogate nipple as a function of prenatal treatments and neonatal conditioning procedures. The data corresponding to ethanol as an unconditioned stimulus employed during postnatal life are representative of collapsed values of 0.25, 0.50, and 0.75 g/kg ethanol. Vertical lines represent the standard errors of the means (adapted from Ref. 115).

Figure 5

Mean intake scores of a low concentrated ethanol solution (0.22% [v/v]). The solution was intraorally delivered at postnatal days 15 and 16. Pups at this age have the capability to ingest or reject intraorally delivered liquids. Intake scores are operationalized through the percentage of increases in the pups’ body weights. These scores were calculated as follows: 100×[(postinfusion weight – preinfusion weight) ÷ preinfusion weight]. Groups are defined as a function of prenatal and postnatal experiences with ethanol (water-water, water-ethanol [EtOH], EtOH-water or EtOH-EtOH). Vertical lines represent the standard errors of the means (adapted from Ref. 83).