Delayed mesolimbic system alteration in a developmental animal model of schizophrenia.
Pharmacological and imaging studies indicate that the prefrontal cortex and nucleus accumbens and their dopamine innervation are central elements of the pathophysiology of schizophrenia. Although symptoms typically appear in young adults, a developmental component has been suggested, primarily in the hippocampus. A neonatal hippocampal lesion in rats and monkeys produces changes resembling schizophrenia symptoms only after the animals reach adulthood, indicating that this procedure could be used as a developmental animal model of this disorder. Here, we explored whether the dopamine projection to the nucleus accumbens becomes functionally altered in these animals. In vivo intracellular recordings revealed abnormal responses in accumbens neurons to activation of their dopamine afferents in adult but not prepubertal animals with a neonatal lesion. This alteration was absent after antipsychotic drug treatment. These results indicate that neonatal hippocampal damage can result in delayed functional deficits in the mesolimbic system, providing a link between the developmental hippocampal deficit and altered dopamine systems postulated to occur in schizophrenia.
Goto
Yukiori
Y
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.
O'Donnell
Patricio
P
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D007051:Ibotenic Acid; D008032:Limbic System / Q000254:growth & development* / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
D018492:Dopamine Antagonists; D007051:Ibotenic Acid; D006220:Haloperidol; D004298:Dopamine