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.
Keywords
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Article info
Publication history
Published online: August 19, 2004
Accepted:
May 28,
2004
Received in revised form:
March 11,
2004
Received:
December 30,
2003
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
