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Locomotor activity in a novel environment predicts vulnerability to drug abuse, yet genetic and environmental influences remain unclear. Using inbred C57BL/6J mice, this thesis examined environmental contributions to individual differences in novelty-induced locomotion. Mice were classified as high responders (HR) or low responders (LR) and compared across neurochemical and hormonal measures. HRs and LRs showed distinct regulation of medial prefrontal cortex glutamate, differing in presynaptic and extracellular glutamate responses, including differential sensitivity to repeated phencyclidine administration. In contrast, corticosterone responses to novelty did not differ between groups. These findings indicate that novelty-induced locomotor differences are linked to glutamatergic regulation rather than stress reactivity.

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