Prefrontal lesion reverses abnormal mesoaccumbens response in an animal model of schizophrenia.
BACKGROUND
A neonatal hippocampal lesion induces postpubertal behavioral alterations resembling phenomena observed in schizophrenia. We have recently reported that nucleus accumbens neurons exhibit altered response to ventral tegmental area activation, but only when animals with this lesion reach adulthood. Because a prefrontal cortical lesion eliminates postpubertal abnormal behaviors in these animals, we investigated whether altered accumbens responses were reversed with this manipulation.


METHODS
In vivo intracellular recordings were conducted in accumbens neurons in rats that had received neonatal hippocampal lesions combined with either adult prefrontal cortical lesion or sham treatment. Accumbens response to mesolimbic pathway activation was recorded in these animals.


RESULTS
Accumbens neurons from animals with a neonatal hippocampal lesion and an adult prefrontal sham operation still showed altered accumbens response to mesolimbic stimulation. On the other hand, most animals with combined neonatal hippocampal and adult prefrontal lesions exhibited responses similar to those of naïve animals.


CONCLUSIONS
This result suggests that abnormal behaviors in these animals might be related to excessive prefrontal drive of accumbens neurons upon dopamine activation.
Goto
Yukiori
Y
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.
O'Donnell
Patricio
P
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001710:Biotin / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology*
C070614:neurobiotin; D001710:Biotin; D004298:Dopamine