Rat strain differences to fluoxetine in striatal Fos-like proteins

Humans afflicted with mood disorders respond differently to antidepressant drug therapy. Different responses to psychoactive drugs are also observed in rats, and specific strains exhibit substantial differences in gene expression following synaptic activity. We examined the effects of fluoxetine on the induction of Fos-like proteins in Long-Evans and Sprague-Dawley rat brains. Fluoxetine elicited a strong induction of Fos in the striatum of Long-Evans but not Sprague-Dawley rats following acute drug exposure. This effect was specific to fluoxetine as two highly selective serotonin reuptake inhibitors, HD-31 and HD-50, as well as treatment with fenfluramine failed to replicate the observed differences in Fos. These differences in Fos expression between rat strains may represent variability in post-receptor pathways that ultimately mediate the therapeutic actions of fluoxetine.