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Neuropsychopharmacology. 2014 Feb;39(3):538-44. doi: 10.1038/npp.2013.255. Epub 2013 Sep 26.

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

Author information

1
1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Department of Pharmacology and Toxicology and Institute on Addictions, University at Buffalo, Buffalo, NY, USA.
2
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY, USA.
4
Department of Pharmacology and Toxicology and Institute on Addictions, University at Buffalo, Buffalo, NY, USA.
5
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.

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.

PMID:
24067299
PMCID:
PMC3895248
DOI:
10.1038/npp.2013.255
[Indexed for MEDLINE]
Free PMC Article

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