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Behavioural sensitization and enhanced dopamine response in the nucleus accumbens after intravenous cocaine self-administration in mice

Authors

  • Agustin Zapata,

    1. Integrative Neuroscience Section, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore MD 2122, USA
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  • Vladimir I. Chefer,

    1. Integrative Neuroscience Section, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore MD 2122, USA
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  • Robert Ator,

    1. Behavioural Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore MD 2122, USA
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  • Toni S. Shippenberg,

    1. Integrative Neuroscience Section, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore MD 2122, USA
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  • Beatriz A. Rocha

    1. Behavioural Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore MD 2122, USA
    2. Department of Psychiatry, University of Maryland, Maryland Psychiatric Research Center, PO Box 21247, Baltimore, MD 2122, USA
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    • *

      Present address: Department of Pharmacology, Merck Research Laboratories, Rahway, NJ 07065, USA


: Dr Shippenberg, as above.
E-mail: Tshippen@intra.nida.nih.gov

Abstract

The behavioural effects of cocaine are enhanced in animals with a prior history of repeated cocaine administration. This phenomenon, referred to as sensitization, is also associated with an increase in cocaine-evoked extracellular dopamine levels in the nucleus accumbens. Behavioural and neurochemical sensitization has been demonstrated in rats with a prior history of cocaine self-administration and in those that had received experimenter-administered cocaine. Although it is clear that the repeated non-contingent administration also results in behavioural sensitization in the mouse, the issue of whether behavioural and neurochemical sensitization also occur in this species following intravenous cocaine self-administration has not been assessed. The present study used the technique of in vivo microdialysis in conjunction with operant self-administration to characterize cocaine-evoked locomotor activity and dopamine levels in the nucleus accumbens in mice with a prior history of intravenous cocaine self-administration or those that had received yoked infusions of cocaine. Mice that had received contingent or non-contingent infusions of cocaine exhibited an enhanced behavioural response to cocaine and increased cocaine-evoked dopamine levels in the nucleus accumbens. There was no difference between groups in the magnitude of this effect. Prior exposure to cocaine did not modify baseline dopamine levels in the nucleus accumbens. These data demonstrate that mice with previous cocaine self-administration experience show an enhanced behavioural and dopamine response to cocaine in the nucleus accumbens. Furthermore, control over cocaine infusion does not significantly alter the magnitude of the sensitized behavioural and presynaptic dopamine responses observed in response to a challenge dose of cocaine.

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