Human fetal ethanol exposure is strongly associated with ethanol avidity during adolescence. Evidence that intrauterine olfactory experience influences chemosensory-guided postnatal behaviors suggests that an altered response to ethanol odor resulting from fetal exposure may contribute to later abuse risk. Using behavioral and neurophysiological methods, the authors tested whether ethanol exposure via the dam's diet resulted in an altered responsiveness to ethanol odor in infant and adult rats. Compared with controls, (a) fetal exposure tuned the neurophysiologic response of the olfactory epithelium to ethanol odor at some expense to its responsiveness to other odorants in infantile rats-this effect was absent in adults; (b) the neural effect in infantile rats was paralleled by an altered behavioral response to ethanol odor that was specific to this odorant-this effect was also absent in adults; and (c) a significant component of the infantile behavioral effect was attributable to ethanol's effect on the olfactory neural modality. These data provide evidence for an important relationship between prenatal ethanol experience and postnatal behavioral responsiveness to the drug that is modulated or determined by olfactory function. Keywords NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe chemical senses are among the earliest systems to develop (Gottlieb, 1971;Schaal & Orgeur, 1992;Smotherman & Robinson, 1990), and in the chemosensory world of the uterus, they may have a unique salience. This statement is of potential significance to the field of ethanol research given that clinical and epidemiological studies provide strong data for a predictive relationship between prenatal ethanol exposure and the risk for ethanol abuse in adolescent and young adults (Alati et al., 2006;Baer, Bar, Bookstein, Sampson, & Streissguth, 1998;Streissguth, 1998;Yates, Cadoret, Troughton, Steward, & Giunta, 1998).It is well documented that olfactory function is fundamental to regulating a variety of biological processes, such as reproduction, food intake, and different social behaviors. Even communication between conspecific and heterospecific animals relies heavily on the reception and processing of odors produced by body glands and even feces and urine. Given this profound level of functional importance, not surprisingly, experience-induced plasticity in response to odorants is a means by which the olfactory system can be tuned to emphasize the transduction of stimuli that are deemed relevant within the animal's environment (Hudson, 1993(Hudson, , 1999. A variety of data indicate that the olfactory system is plastic in response to the odorant environment and have been gathered using different experimental manipulations, such as selective odorant exposure in neonates (Coopersmith & Leon, 1984;Johnson, Woo, Duong, Nguyen, & Leon, 1995;McCollum, Woo, & Leon, 1997;McLean & Harley, 2004;Sullivan & Leon, 1986;Sullivan, McGaugh, & Leon, 1991;Sullivan, Wilson, & Leon, 1989;Woo, Coopersmith, & Leon, 1987;Wo...

To test the hypothesis that odorant quality perception is altered in olfactory marker protein (OMP)-null mice, we trained and tested adult OMP-null and control mice, using a 5-odorant identification confusion matrix task (animal odorant confusion matrix [AOCM]). On average, control and null mice performed the task at equivalent levels. The composite 5 x 5 response matrix from 40 testing sessions for each subject (both OMP-null and control) was compared with that of every other subject, yielding a dissimilarity matrix of AOCM responses. A multidimensional scaling (MDS) analysis of the dissimilarity data yielded a 4-dimensional solution, with each mouse occupying a point in MDS animal space. Statistical analysis demonstrated significant effects of genotype in determining the location of a mouse in the MDS space. These data suggest, therefore, that compared with that of controls, odorant quality perception is altered in the OMP-null mouse.

Clinical and epidemiological studies provide strong data for a relationship between prenatal ethanol exposure and the risk for abuse in adolescent and young adult humans. However, drugacceptance results in response to fetal exposure have differed by study, age at evaluation, and experimental animal. In the present study, the authors tested whether voluntary ethanol intake was enhanced in both the infantile and adult rat (15 and 90 days of age, respectively), as a consequence of chronic fetal drug experience. Experimental rats were exposed in utero by administering ethanol to a pregnant dam in a liquid diet during gestational Days 6-20. Compared with those for isocaloric pair-fed and ad lib chow control animals, the results for experimental animals demonstrated that fetal exposure significantly increased infantile affinity for ethanol ingestion without affecting intake patterns of an alternative fluid (water). Heightened affinity for ethanol was absent in adulthood. Moreover, the results argue against malnutrition as a principal factor underlying the infantile phenomenon. These data add to a growing literature indicative of heightened early postnatal acceptance patterns resulting from maternal use or abuse of ethanol during pregnancy. Keywordsfetal ethanol exposure; postnatal ethanol affinity; ethanol abuse; ethanol drinking behavior; fetal learning It has been well established that prenatal exposure to ethanol can exert profound detrimental effects in the developing fetus. The effects can be widespread, severe, and generally permanent. Depending on timing of exposure, and its duration and dose, these include stereotypical craniofacial malformations, poor suckling reflexes, decreased birth weight NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript (Abel & Hannigan, 1995;Astley, Clarren, Little, Sampson, & Daling, 1992;Clareen & Smith, 1978;Jones, Smith, Ulleland, & Streissguth, 1973; Lemoine, Harousseau, Borteyru, & Meneut, 1968;Martin, Martin, Streissguth, & Lund, 1977;Osborn, Harris, & Weinberg, 1993;Oulette, Rosett, Rosman, & Weiner, 1977;Streissguth, Landesman-Dwyer, Martin, & Smith, 1980;Ulleland, Wennburg, Igo, & Smith, 1970;Van Dyke, MacKay, & Ziaylek, 1982), and other profound neurodevelopmental effects in the nervous system Miller, 1992b). Prenatal exposure to ethanol can cause behavioral changes, such as hyperactivity, and learning and memory deficits: Indeed, gestational exposure is a leading known cause of mental retardation (Abel & Hannigan, 1995;Abel & Sokol, 1992;Sampson et al., 1997;Stratton, Howe, & Battaglia, 1996).The above notwithstanding, there are subtler yet potentially just as detrimental long-term consequences. Recent clinical and epidemiological studies indicate that prenatal exposure to ethanol is strongly associated with the risk for ethanol abuse in adolescent and young adult humans (Alati et al., 2006;Baer, Bar, Bookstein, Sampson, & Streissguth, 1998;Streissguth, 1998;Yates, Cadoret, Troughton, Steward, & Giunta, 1998). In effect, gestational exposure...

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BackgroundAn 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.MethodsPregnant 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.ResultsExperiment 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.ConclusionFetal 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.