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Brain cholecystokinin (CCK) and its receptor CCK(2) have been implicated in the etiology of anxiety. CCK(2) antagonists, however, fail to ameliorate anxiety in humans. In this study, a role for CCK in adaptation to stress is investigated by testing carry-over effects of Ly225.910, a potent CCK(2) antagonist, in a rat model of individual differences in novelty-induced emotionality. Novelty-seeking behavior in the rat is thought to model some aspects of sensation-seeking, a personality trait closely associated with risk activities including substance abuse. Animals were categorized as high-responders (HR) and low-responders (LR) based on the activity response to an inescapable novel environment. High-responders exhibit increased exploration and proactive behavior while low-responders are less exploratory and deemed to behave more anxiously. We analyzed the effects of the CCK(2) antagonist Ly225.910 (0.1mg/kg …