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

Background: Increased substance disorder comorbidity in schizophrenia may reflect greater vulnerability to addictive processes because of inherent neurocircuit dy, function in the schizophrenic brain. Methods: To further explore this bypothesis, 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 inection 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In a neurodevelopmental model of schizophrenia, the locomotor effects of cocaine were augmented on initial and repealed doses, with emergence of irregularity in sensitization-related changes in activity in the short term and perseverance of augmented effects in the long term.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 ststems dysfunction responsible for major psychiatric syndromes.