DeltaFosB Induction in HUMAN Prefrontal Cortex by Antipsychotic Drugs is Associated with Negative Behavioral Outcomes (2013)

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Neuropsychopharmacology. 2013 Sep 26. doi: 10.1038/npp.2013.255.

Dietz DM, Kennedy PJ, Sun H, Maze I, Gancarz AM, Vialou V, Koo J, Mouzon E, Ghose S, Tamminga CA, Nestler EJ.

Source

1]
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn
School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York,
NY, USA [2] Department of Pharmacology and Toxicology and Institute on
Addictions, University at Buffalo, Buffalo, New York, 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 has not been explored. Here, we assessed whether ΔFosB induction by haloperidol mediates the negative consequences or clinical-related efficacy 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 ?FosB in the PFC of rodents induced cognitive deficits as measured by inhibitory avoidance, increased startle responses in PPI tasks, and increased MK-801-induced anxiety-like behaviors. Together, these results suggest that ?FosB induction in PFC by antipsychotic treatment contributes to the deleterious effects of these drugs and not to their therapeutic actions.Neuropsychopharmacology accepted article preview online, 26 September 2013. doi:10.1038/npp.2013.255.