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Prefrontal lesion reverses abnormal mesoaccumbens response in an animal model of schizophrenia

  • Yukiori Goto
    Affiliations
    Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York, USA
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  • Patricio O'Donnell
    Correspondence
    Address reprint requests to Patricio O'Donnell, M.D., Ph.D., Albany Medical College (MC-136), Center for Neuropharmacology and Neuroscience, 47 New Scotland Avenue, Albany NY 12208, USA.
    Affiliations
    Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York, USA
    Search for articles by this author

      Abstract

      Background

      A neonatal hippocampal lesion induces postpubertal behavioral alterations resembling phenomena observed in schizophrenia. We have recently reported that nucleus accumbens neurons exhibit altered response to ventral tegmental area activation, but only when animals with this lesion reach adulthood. Because a prefrontal cortical lesion eliminates postpubertal abnormal behaviors in these animals, we investigated whether altered accumbens responses were reversed with this manipulation.

      Methods

      In vivo intracellular recordings were conducted in accumbens neurons in rats that had received neonatal hippocampal lesions combined with either adult prefrontal cortical lesion or sham treatment. Accumbens response to mesolimbic pathway activation was recorded in these animals.

      Results

      Accumbens neurons from animals with a neonatal hippocampal lesion and an adult prefrontal sham operation still showed altered accumbens response to mesolimbic stimulation. On the other hand, most animals with combined neonatal hippocampal and adult prefrontal lesions exhibited responses similar to those of naïve animals.

      Conclusions

      This result suggests that abnormal behaviors in these animals might be related to excessive prefrontal drive of accumbens neurons upon dopamine activation.

      Keywords

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