The consequence of fetal ethanol exposure and adolescent odor re-exposure on the response to ethanol odor in adolescent and adult rats

Background: An epidemiologic predictive relationship exists between fetal ethanol exposure and the likelihood for adolescent use. Further, an inverse relationship exists between the age of first experience and the probability of adult abuse. Whether and how the combined effects of prenatal and adolescent ethanol experiences contribute to this progressive pattern remains unknown. Fetal ethanol exposure directly changes the odor attributes of ethanol important for both ethanol odor preference behavior and ethanol flavor perception. These effects persist only to adolescence. Here we tested whether adolescent ethanol odor re-exposure: (Experiment 1) augments the fetal effect on the adolescent behavioral response to ethanol odor; and/or (Experiment 2) perpetuates previously observed adolescent behavioral and neurophysiological responses into adulthood. Methods: Pregnant rats received either an ethanol or control liquid diet. Progeny (observers) experienced ethanol odor in adolescence via social interaction with a peer (demonstrators) that received an intragastric infusion of either 1.5 g/kg ethanol or water. Social interactions were scored for the frequency that observers followed their demonstrator. Whole-body plethysmography evaluated the unconditioned behavioral response of observers to ethanol odor in adolescence (P37) or adulthood (P90). The olfactory epithelium of adults was also examined for its neural response to five odorants, including ethanol. Results: Experiment 1: Relative to fetal or adolescent exposure alone, adolescent re-exposure enhanced the behavioral response to ethanol odor in P37 animals. Compared to animals with no ethanol experience, rats receiving a single experience (fetal or adolescent) show an enhanced, yet equivalent, ethanol odor response. Fetal ethanol experience also increased olfactory-guided following of an intoxicated peer. Experiment 2: Combined exposure yielded persistence of the behavioral effects only in adult females. We found no evidence for persistence of neurophysiological effects in either sex. Conclusion: Fetal ethanol exposure influences adolescent re-exposure, in part, by promoting interactions with intoxicated peers. Re-exposure subsequently enhances ethanol odor responsivity during a key developmental transition point for emergent abuse patterns. While persistence of behavioral effects occurred in females, the level of re-exposure necessary to uniformly yield persistence in both sexes remains unknown. Nonetheless, these results highlight an important relationship between fetal and adolescent experiences that appears essential to the progressive pattern of developing ethanol abuse.