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Animal models also demonstrate associations between novelty responsiveness or early life stress and increased sensitivity to psychostimulants. We investigated whether repeated maternal separation affects responses to novelty during adolescence and to amphetamine during adulthood, and whether maternal separation alters the relationship between these behavioral variables. Rat pups underwent separation (180\u2009min\/day) or control procedures (15\u2009min\/day) on postnatal days (PND) 2\u20138. Novel object exploration and amphetamine response were tested at PND 38 and 60, respectively. Adolescent males were less active in a novel environment and approached novel objects more frequently than females, but adult females showed greater amphetamine\u2010induced locomotion. Maternal separation did not affect novelty responsiveness or amphetamine sensitivity. Locomotor activity in an inescapable, novel environment during adolescence predicted amphetamine\u2010induced locomotor activity during adulthood in maternally separated rats, but not in controls. The results of this study suggest that adolescent responses to novelty may be particularly predictive of future substance abuse among survivors of early life trauma. Furthermore, sex differences in novelty and amphetamine responsiveness may complicate the relationship between these behavioral variables. \u00a9 2010 Wiley Periodicals, Inc. 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