Comparison of Alterations in c-fos and Egr-1 (zif268) Expression Throughout the Rat Brain Following Acute Administration of Different Classes of Antidepressant Compounds

Abstract

The majority of immediate-early gene (IEG) studies focus on a few key brain regions associated with the class of psychoactive compound being studied. Recently, using a meta-analysis of the c-fos literature, we demonstrated the utility of c-fos profiling to classify such compounds. The present study examined acute delivery of a range of antidepressant classes; fluoxetine, imipramine, LiCl, and mirtazapine. The dual aims were to study the IEG profiles of these varying classes of antidepressants throughout the rat brain and to compare the utility of c-fos or Egr-1 as IEGs to classify clinically efficacious antidepressants. All antidepressants increased c-fos mRNA in the central amygdala, as previously shown, while c-fos was also increased in the anterior insular cortex and significantly decreased within the septum. Although acute antidepressant administration altered c-fos expression in a number of brain regions, Egr-1 expression was only significantly altered in the central amygdala, suggesting that Egr-1 may not be as useful a marker to investigate acute antidepressant treatment. The fact that these drugs, including the previously unclassified antidepressant mirtazapine, share a number of common loci of activation, which are implicated by human and animal studies in depression, adds further support to the use of IEG mapping to classify psychoactive compounds.

Induction of c-Fos and ΔFosB Immunoreactivity in Rat Brain by Vagal Nerve Stimulation

“…Essentially all studies were conducted after acute (30 min-2 h) administration of antidepressants. A reasonably consistent observation is that administration of pharmacologically diverse antidepressants (SSRIs, selective NRIs, MAOIs, mirtazapine) increase c-fos or c-Fos in the central nucleus of the amygdala (CeA) and BNST (Beck, 1995;Duncan et al, 1996;Fraga et al, 2005;Miyata et al, 2005;Morelli et al, 1999;Slattery et al, 2005;Sumner et al, 2004;Thomsen and Helboe, 2003). This increase was also seen in female rats treated acutely with fluoxetine (Torres et al, 1998).…”

“…Most studies report no increase in the DRN, although Fraga et al (2005) did find an increase after administration of fluoxetine. When increases in the LC have been reported, it has been upon administration of the SSRI fluoxetine (Fraga et al, 2005;Slattery et al, 2005;Sumner et al, 2004) but, with one exception (Beck, 1995), not with other types of antidepressants. In general, increases have not been reported in the hippocampus and many other regions of brain and effects in cortical areas have been quite inconsistent.…”

Comparison of ΔFosB Immunoreactivity Induced by Vagal Nerve Stimulation with That Caused by Pharmacologically Diverse Antidepressants

“…Somewhat surprisingly, administration of fluoxetine (Fraga et al, 2005;Slattery et al, 2005) but not other types of antidepressants, with one exception (Ková cs, 1998), was found to increase c-Fos in the LC. In general, increases have not been reported in the DRN although Fraga et al (2005) found an increase after short-term administration of fluoxetine.…”

“…In general, increases have not been reported in the DRN although Fraga et al (2005) found an increase after short-term administration of fluoxetine. Most studies show increases in c-fos or c-Fos in the CeA and BNST after short-term administration of different classes of antidepressants (Beck, 1995;Fraga et al, 2005;Slattery et al, 2005;Bechtholt et al, 2008). Longterm treatment of rats with either paroxetine (Muigg et al, 2007) or citalopram (Kuipers et al, 2006) did not increase c-Fos in any brain region examined, including the CeA.…”

“…Several studies have examined mRNA for c-fos or c-Fos protein after antidepressant treatments, with the majority studying short-term effects (Beck, 1995;Fraga et al, 2005;Slattery et al, 2005). Data from these studies have been inconsistent with respect to activation in the dorsal raphe nucleus (DRN), locus ceruleus (LC), hippocampus, and cortical areas of brain.…”