Altered prefrontal cortical metabolic response to mesocortical activation in adult animals with a neonatal ventral hippocampal lesion.
BACKGROUND
Adult animals with a neonatal ventral hippocampal lesion (NVHL) exhibit deficits in working memory and sensorimotor gating similar to those observed in schizophrenia. As cognitive deficits in this disorder are typically associated with changes in cortical metabolic levels, we investigated here whether an NVHL affects metabolic responses to ventral tegmental area (VTA) activation, a procedure that elicits abnormal cell firing in the prefrontal cortex (PFC) of NVHL animals.


METHODS
Prefrontal cortex metabolic activity was determined by measuring cytochrome oxidase I (CO-I) staining. Cytochrome oxidase I levels were quantified by densitometry in pre- and postpubertal sham-operated and lesioned rats that received one or three series of fifteen 20-Hz trains of VTA stimuli every 20 seconds.


RESULTS
Ventral tegmental area stimulation yielded higher levels of PFC CO-I in NVHL animals when compared with the sham-operated group, an effect that appeared only after puberty. Increasing the series of burst stimulations further elevated CO-I in sham-operated, but not in NVHL animals.


CONCLUSIONS
Increased PFC CO-I activity after VTA burst stimulation in NVHL rats highlights the enhanced energy demand that could be linked to the exaggerated response to stress observed in these animals. The inability to further increase the response with higher mesocortical activity, as observed in sham-operated animals, could be expression of a reduced PFC functional capacity in lesioned animals. Thus, a hyperexcitable PFC with a reduced ability to further increase activity could be a plausible pathophysiological scenario for schizophrenia. Human functional studies could be interpreted in the light of this conceptual framework.
Tseng
Kuei Y
KY
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA. tsengky@mail.amc.edu
Amin
Fatema
F
Lewis
Barbara L
BL
O'Donnell
Patricio
P
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001930:Brain Injuries / Q000473:pathology*; D004558:Electric Stimulation / Q000379:methods; D003576:Electron Transport Complex IV / Q000378:metabolism; D007839:Functional Laterality; D006624:Hippocampus / Q000254:growth & development / Q000503:physiopathology*; D006651:Histocytochemistry / Q000379:methods; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000503:physiopathology* / Q000528:radiation effects
D003576:Electron Transport Complex IV