Schizophrenia Bulletin Advance Access published online on May 24, 2007
Schizophrenia Bulletin, doi:10.1093/schbul/sbm039
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Injections of NGF Into Neonatal Frontal Cortex Decrease Social Interaction as Adults: A Rat Model of Schizophrenia
2 Department of Psychology, University of Western Ontario, Social Science Centre, 1151 Richmond Street, London, Ontario, Canada N6A 5C2
3 Department of Psychiatry, University of Western Ontario, Medical Sciences Building, 1151 Richmond Street, London, Ontario, Canada N6A 5C1
4 Graduate Program in Neuroscience, University of Western Ontario, Social Science Centre, 1151 Richmond Street, London, Ontario, Canada N6A 5C2
1 To whom correspondence should be addressed; tel: +1-519-661-2111, fax: +1-519-850-2517, e-mail: nlazar{at}uwo.ca.
Background: Injection of nerve growth factor (NGF) into the developing frontal cortex (FC) has been shown to produce adult-onset subcortical dopaminergic hyperactivity, impaired prepulse inhibition of the acoustic startle response, and several neuropathological features of schizophrenia. The present study was to determine whether such lesions would lead to impaired social interaction, a prominent negative feature of schizophrenia. Methods: Rat pups received daily injections of human recombinant NGF into the developing FC on postnatal days 1 and 2 to partially lesion subplate neurons. Lesioned rats were tested in similar-treatment pairings lasting 23.5 hours using the EthoVision behavioral monitoring system at 6 and 14 weeks of age. Brains were then perfusion fixed for histological analysis. Results: Lesioned rats showed significantly increased movement, relative to controls, during the light phase at 6 weeks of age. At 14 weeks, they maintained a significantly greater mean distance apart from one another, and engaged in significantly less approach and avoidance behavior during the dark phase, relative to controls. Histological changes were consistent with those described previously in this animal model. Conclusion: Results indicate that injections of NGF into the developing FC of neonatal rats result in reduced social interaction, which is consistent with behaviors observed in human schizophrenia patients.
Keywords: animal model / social withdrawal / EthoVision / mean distance apart / approach behavior / avoidance behavior