EN
The sites of action of antidepressants in the brain responsible for their psychotropic effects are not fully elucidated. Our study was undertaken to compare acute effects of antidepressants representing diverse modes of molecular action on regional brain activity, reflected by expression of immediate-early genes (IEG). In situ hybridization was used to analyze expression of the IEG Fos, Egr1 and Arc in the mouse forebrain after a single injection of tranylcypromine (MAO inhibitor), mianserin (acting on 5-HT, NA and histamine receptors but not on monoamine levels) and tianeptine (with unknown molecular targets). Tranylcypromine and tianeptine produced a widespread IEG induction in the neocortex and striatum (where mianserin down-regulated IEG). The similarity of the tianeptine and tranylcypromine effects suggests that elevation of monoamine levels is an important mechanism by which tianeptine affects forebrain function. Moreover, all three drugs elicited IEG induction in several brain regions implicated in the regulation of mood in humans: anterior cingulate and insular cortex, basolateral amygdala and paraventricular thalamic nucleus. The common activation of these regions by different types of antidepressants suggests that they may be the sites where neuroplastic changes take place upon chronic drug treatment, leading to the long-term psychotropic effect.