Perhaps the best predictor of ethanol abuse in adolescence and young adult humans is prior fetal exposure to the drug. Yet, there is a relative paucity of evidence regarding the factors contributing to these long-term ingestive consequences. Studies have demonstrated that olfactory experience influences behavioral and neural sensory function; that postnatal behaviors controlled by odor stimuli are influence d by intrauterine experiences; and these experiences can be retained into adulthood, modulating intake and preference patterns. Taken together, these observations support the innovative central hypothesis of this proposal, that what the fetus learns from ethanol contamination of the prenatal environment is facilitated by a behavioral and neurophysiologic """"""""tuning"""""""" of the olfactory system that contribute s to the later risk for preference and abuse. In support of this proposition, we provide compelling preliminary evidence that: (1) clinically relevant in utero exposure to ethanol focuses the neurophysiologic response of the olfactory system to ethanol odor at some expense to the generally broad responsivity of the system; (2) the effect was evident in the early postnatal anima l and that it persisted into adulthood; and (3) the observed neurophysiologic """"""""tuning"""""""" to ethanol was associated wit h an alteration in the behavioral response to ethanol odor in both age groups. Thus, the long-range goal associated wit h this research program is to analyze fetal experience with ethanol in terms of its affect on an organism' s later chemosensory perception and odor-guided response to ethanol ; and to understand the mechanism s underlying the neural and behavioral effects in olfactory function related to altered odor-guided recognition and acceptance patterns of thi s drug. Guide d by our strong preliminary data, the objective of this particular application is to apply a set of interdisciplinary technique s (i.e., behavioral, neurophysiologic and anatomical) to test two specific aims: (1) we will test the hypothesis that prenatal ethanol exposure results in an altered odor-guided and drug-seeking behavioral responsiveness to ethanol that is mediated by an enhanced neurophysiologic response of the olfactory epithelium to this odorant, in both early postnatal and adult animals; and (2) we will test the hypothesis that enhanced or """"""""tuned"""""""" olfactory bulb activation to ethanol odor and changes in specific bulbar structures mediate the experience-based alterations of the response of the olfactory periphery . The proposed research is significant, because it is expected to advance and expand our understanding of the factors contributing to the initiation of ethanol intake. An understanding of these processes will facilitate the development and testing of preventive and therapeutic strategies. It will also establish a chemosensory related conceptual framework of fetal exposure with broad based importance in child development and drug abuse.
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