Antipsychotic drugs modulate Arc expression in the rat brain.

We found that, in the striatum, acute injections of the first generation antipsychotic (FGA) haloperidol or the second generation antipsychotic (SGA) olanzapine enhanced Arc mRNA levels, however such induction persisted for at least 2 h in haloperidol-treated rats whereas it waned as early as 1 h after olanzapine injection. Conversely, repeated injections led to a persistent decrease of striatal Arc gene expression, regardless of the agent examined. In the frontal cortex, acute injection of both antipsychotics caused a reduction of Arc mRNA levels which persisted for at least 2 h. Following repeated treatment, olanzapine reduced Arc mRNA levels 2 h, but not 24 h, post-treatment whereas haloperidol was ineffective. Of note, the SGA quetiapine regulated the Arc gene expression similarly to olanzapine. Given the particular nature of Arc, our findings show its fine tuning following antipsychotic administration to be highly dependent on the length of the treatment and on the brain region investigated and suggest that antipsychotic drugs affect this marker of neuronal activity differently.