Research Article| Volume 56, ISSUE 5, P308-316, September 01, 2004

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Animal modeling dual diagnosis schizophrenia: Sensitization to cocaine in rats with neonatal ventral hippocampal lesions

  • R. Andrew Chambers
    Address reprint requests to R. Andrew Chambers, M.D., Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202
    Laboratory for Translational Neuroscience of Dual Diagnosis Disorders (RAC), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana
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  • Jane R. Taylor
    Division of Molecular Psychiatry (JRT), Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA
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      Increased substance disorder comorbidity in schizophrenia may reflect greater vulnerability to addictive processes because of inherent neurocircuit dysfunction in the schizophrenic brain.


      To further explore this hypothesis, we used neonatal ventral hippocampal lesions (NVHL) as a rat model of schizophrenia and assessed locomotor sensitization to cocaine (15 mg/kg) in adulthood.


      The NVHL animals showed greater activity in response to an initial cocaine injection compared with sham and saline-treated groups. With daily cocaine injections over 7 days, NVHL rats showed elevated locomotor sensitization curves with greater fluctuations in the intersession changes in activity between days 4 and 7. In a single session 4 weeks later, NVHL compared with SHAM rats showed maintenance of cocaine-associated hyperactivity, as if superimposed on long-term sensitization effects present in both groups.


      In a neurodevelopmental model of schizophrenia, the locomotor effects of cocaine were augmented on initial and repeated doses, with emergence of irregularity in sensitization-related changes in activity in the short term and perseverance of augmented effects in the long term. Altered patterns of behavioral sensitization, as a possible correlate of greater addiction vulnerability, can occur as a by-product of neural systems dysfunction responsible for major psychiatric syndromes.


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