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

R. Andrew Chambers, Jane R. Taylor

Research output: Contribution to journalArticle

42 Scopus citations


Background: Increased substance disorder comorbidity in schizophrenia may reflect greater vulnerability to addictive processes because of inherent neurocircuit dysfunction in the schizophrenic brain. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)308-316
Number of pages9
JournalBiological psychiatry
Issue number5
StatePublished - Sep 1 2004


  • Cocaine
  • dual diagnosis
  • locomotor sensitization
  • schizophrenia
  • substance use disorders
  • ventral hippocampus

ASJC Scopus subject areas

  • Biological Psychiatry

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