ΔfosB induction in prefrontal cortex by antipsychotic drugs is associated with negative behavioral outcomes

David M. Dietz, Pamela J. Kennedy, Haosheng Sun, Ian Maze, Amy M. Gancarz, Vincent Vialou, Ja Wook Koo, Ezekiell Mouzon, Subroto Ghose, Carol A. Tamminga, Eric J. Nestler

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

ΔFosB, a FosB gene product, is induced in the prefrontal cortex (PFC) by repeated exposure to several stimuli including antipsychotic drugs such as haloperidol. However, the functional consequences of increased ΔFosB expression following antipsychotic treatment have not been explored. Here, we assessed whether ΔFosB induction by haloperidol mediates the positive or negative consequences or clinical-related actions of antipsychotic treatment. We show that individuals with schizophrenia who were medicated with antipsychotic drugs at their time of death display increased ΔFosB levels in the PFC, an effect that is replicated in rats treated chronically with haloperidol. In contrast, individuals with schizophrenia who were medication-free did not exhibit this effect. Viral-mediated overexpression of ΔFosB in the PFC of rodents induced cognitive deficits as measured by inhibitory avoidance, increased startle responses in prepulse inhibition tasks, and increased MK-801-induced anxiety-like behaviors. Together, these results suggest that ΔFosB induction in the PFC by antipsychotic treatment contributes to the deleterious effects of these drugs and not to their therapeutic actions.

Original languageEnglish (US)
Pages (from-to)538-544
Number of pages7
JournalNeuropsychopharmacology
Volume39
Issue number3
DOIs
StatePublished - Feb 1 2014

Keywords

  • G9a
  • MK801
  • amphetamine
  • haloperidol
  • inhibitory avoidance
  • prepulse inhibition
  • transcription factors

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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    Dietz, D. M., Kennedy, P. J., Sun, H., Maze, I., Gancarz, A. M., Vialou, V., Koo, J. W., Mouzon, E., Ghose, S., Tamminga, C. A., & Nestler, E. J. (2014). ΔfosB induction in prefrontal cortex by antipsychotic drugs is associated with negative behavioral outcomes. Neuropsychopharmacology, 39(3), 538-544. https://doi.org/10.1038/npp.2013.255