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Discriminative Inhibitory Control of Cocaine Seeking Involves the Prelimbic Prefrontal Cortex

  • Claudia Mihindou
    Affiliations
    Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, Bordeaux, France
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  • Author Footnotes
    1 Authors KG and SN Contributed equally to this work.
    Karine Guillem
    Footnotes
    1 Authors KG and SN Contributed equally to this work.
    Affiliations
    Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, Bordeaux, France
    Search for articles by this author
  • Author Footnotes
    1 Authors KG and SN Contributed equally to this work.
    Sylvia Navailles
    Footnotes
    1 Authors KG and SN Contributed equally to this work.
    Affiliations
    Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, Bordeaux, France
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  • Caroline Vouillac
    Affiliations
    Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, Bordeaux, France
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  • Serge H. Ahmed
    Correspondence
    Address correspondence to Serge H. Ahmed, Ph.D., Université Bordeaux-Segalen, Institut des Maladies Neurodégénératives/CNRS UMR 5293, 146 rue Léo-Saignat, Bordeaux 33076, France
    Affiliations
    Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, Bordeaux, France
    Search for articles by this author
  • Author Footnotes
    1 Authors KG and SN Contributed equally to this work.
Published:September 17, 2012DOI:https://doi.org/10.1016/j.biopsych.2012.08.011

      Background

      Recent neuroimaging studies have shown that people with cocaine addiction retain some degree of control over drug craving that correlates with neural activity in the lateral prefrontal cortex (PFC). Here, we report similar findings in a rat model of inhibitory control of cocaine seeking.

      Methods

      Rats actively responding for cocaine were trained to stop responding when presented with a discriminative stimulus that signaled lack of reinforcement. Rats were then tested for inhibitory control of cocaine seeking in novel behavioral contexts and in circumstances when cocaine seeking is particularly intense (e.g., following drug priming). The role of neuronal activity in different subregions of the PFC was assessed using local pharmacologic inactivation and c-Fos immunohistochemistry.

      Results

      Rats progressively acquired the ability to stop cocaine seeking, even during drug intoxication and after a long history of cocaine self-administration. Inhibitory control of cocaine seeking was flexible, sufficiently strong to block cocaine-primed reinstatement, and selectively depended on increased neuronal activity within the prelimbic PFC, which is considered the rodent functional homolog of the human lateral PFC.

      Conclusions

      Parallel evidence in both animal models and humans indicate that recruitment of prefrontal inhibitory control of drug seeking is still functional after prolonged cocaine use. Preclinical investigation of the mechanisms underlying this capacity may contribute to designing new behavioral and/or pharmacologic strategies to promote its use for the prevention of relapse in addiction.

      Key Words

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