Neonatal ventral hippocampal lesions produce an elevation of ΔFosB-like protein(s) in the rodent neocortex

Kelly J. Powell, Tammy L. Binder, Sarah Hori, Yusaku Nakabeppu, Daniel R. Weinberger, Barbara K. Lipska, George S. Robertson

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16 Citations (Scopus)

Abstract

Rats that have sustained bilateral excitotoxic lesions of the ventral hippocampus (VH) as neonates develop behavioral abnormalities as adults (hyper-responsiveness to stress, diminished prepulse inhibition, and increased sensitivity to dopamine agonists), which resemble certain aspects of schizophrenia. Although this behavioral profile is thought to reflect dysregulation of the mesolimbic dopamine system, the precise neuroanatomical and neurochemical substrates that mediate the emergence of these abnormalities during brain maturation are unclear. In order to identify putative sites responsible for the development of behavioral abnormalities following neonatal lesions of the VH, we utilized the chronic neuronal activity marker ΔFosB. By comparison to sham lesioned animals, bilateral destruction of the VH elevated ΔFosB expression throughout the caudate putamen and neocortex of animals lesioned as neonates. These increases were not observed in rats lesioned as young-adults, suggesting that ΔFosB induction in the cortex of neonatally lesioned rats may be related to altered cortical neurodevelopment. Accumulating evidence implicates ΔFosB in mediation of the long-lasting effects of altered dopaminergic neurotransmission on behavior. The present findings are consistent with this proposal and suggest that elevated expression of ΔFosB identifies overactive neurons that may contribute to the enhanced sensitivity to stress and dopaminergic agonists of rats that have sustained bilateral ventral hippocampal lesions as neonates.

Original languageEnglish
Pages (from-to)700-711
Number of pages12
JournalNeuropsychopharmacology
Volume31
Issue number4
DOIs
Publication statusPublished - Apr 1 2006

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

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