There are noticeable differences in the amount of drug exposure necessary for individual animals and humans to become addicted. A subject's locomotor response to a novel environment appears to predict vulnerability to psychomotor stimulants. The proposed experiments are designed to determine the specific neuroanatomical areas of the mesolimbic system responsible for individual differences in vulnerability to amphetamine. The areas of the mesolimbic system to be examined are the ventral tegmental area (VTA), nucleus accumbens (NACC), and medial frontal cortex (MFC) since they primarily mediate the behavioral responses to drugs such as amphetamine and to novelty. The role of dopamine in these regions in determining individual vulnerability to amphetamine will also be examined. The proposed project consists of one behavioral and two neurochemical experiments to determine individual vulnerability to drugs of abuse. The first experiment uses behavioral measures following repeated intracranial administration of amphetamine and a subsequent systemic challenge to determine which neuroanatomical structures are most responsible for differences in sensitization to the drug. The two neurochemical experiments are designed to use in vivo microdialysis to determine differences in dopaminergic basal state and responsiveness in the VTA, NACC, and MFC. These experiments will provide detailed information about the role of neuroanatomical and neurochemical basis of vulnerability to drugs of abuse.
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