Injections of NGF into neonatal frontal cortex decrease social interaction as adults: a rat model of schizophrenia.
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.


CONCLUSIONS
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.
Lazar
Noah L
NL
Department of Psychology, University of Western Ontario, Ontario, Canada. nlazar@uwo.ca
Rajakumar
Nagalingam
N
Cain
Donald Peter
DP
D000367:Age Factors; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D007267:Injections; D008124:Locomotion / Q000187:drug effects; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000139:chemically induced* / Q000503:physiopathology; D012919:Social Behavior
D020932:Nerve Growth Factor