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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National Institute on Drug Abuse (NIDA)
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Drug Abuse Biomedical Research Review Committee (DABR)
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Emory University
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Schad, Christina A; Justice Jr, Joseph B; Holtzman, Stephen G (2002) Endogenous opioids in dopaminergic cell body regions modulate amphetamine-induced increases in extracellular dopamine levels in the terminal regions. J Pharmacol Exp Ther 300:932-8
Gong, W; Justice Jr, J B; Neill, D (1997) Dissociation of locomotor and conditioned place preference responses following manipulation of GABA-A and AMPA receptors in ventral pallidum. Prog Neuropsychopharmacol Biol Psychiatry 21:839-52
Gong, W; Neill, D B; Justice Jr, J B (1996) Locomotor response to novelty does not predict cocaine place preference conditioning in rats. Pharmacol Biochem Behav 53:191-6
Schad, C A; Justice Jr, J B; Holtzman, S G (1996) Differential effects of delta- and mu-opioid receptor antagonists on the amphetamine-induced increase in extracellular dopamine in striatum and nucleus accumbens. J Neurochem 67:2292-9
Gong, W; Neill, D; Justice Jr, J B (1996) Conditioned place preference and locomotor activation produced by injection of psychostimulants into ventral pallidum. Brain Res 707:64-74
Schad, C A; Justice Jr, J B; Holtzman, S G (1995) Naloxone reduces the neurochemical and behavioral effects of amphetamine but not those of cocaine. Eur J Pharmacol 275:9-16
Gong, W; Neill, D B; Justice Jr, J B (1995) Increased sensitivity to cocaine place-preference conditioning by septal lesions in rats. Brain Res 683:221-7
Hooks, M S; Jones, G H; Juncos, J L et al. (1994) Individual differences in schedule-induced and conditioned behaviors. Behav Brain Res 60:199-209
Jones, G H; Hooks, M S; Juncos, J L et al. (1994) Effects of cocaine microinjections into the nucleus accumbens and medial prefrontal cortex on schedule-induced behaviour: comparison with systemic cocaine administration. Psychopharmacology (Berl) 115:375-82
Hooks, M S; Jones, D N; Holtzman, S G et al. (1994) Individual differences in behavior following amphetamine, GBR-12909, or apomorphine but not SKF-38393 or quinpirole. Psychopharmacology (Berl) 116:217-25

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