Contrasting Fos expression induced by acute reboxetine and fluoxetine in the rat forebrain: neuroanatomical substrates for the antidepressant effect

Rationale Antidepressants preferentially facilitating serotonin seem to be particularly effective for treating the anxiety and aggressive component of the depressive syndrome, whereas those with a noradrenergic profile seem to be more effective in reducing psychomotor retardation, although their overall antidepressant effects are about the same. However, the mechanism of this difference remains unknown.Objectives To investigate the neural substrate for the different therapeutic efficacies of fluoxetine and reboxetine, we examined the regional Fos immunoreactivity (Fos-ir) induced by the two agents.Methods Male Wistar rats (290–330 g) were given a subcutaneous injection of fluoxetine (5 or 10 mg/kg), reboxetine (5 or 10 mg/kg) or saline. Two hours later, rats were perfused through the ascending aorta and their brains were processed for Fos immunohistochemistry. Fos-ir was quantified by counting the number of Fos-ir-positive nuclei in six areas of the forebrain.Results The shell of the nucleus accumbens was the only region in which both fluoxetine and reboxetine equally increased Fos-ir expression. Fluoxetine particularly induced Fos-ir in the central nucleus of the amygdala. In contrast, reboxetine induced Fos-ir in the cingulate cortex area 3 and the lateral orbital cortex.Conclusions These results suggest that the shell region may be one possible target for the antidepressant effects of fluoxetine and reboxetine. Furthermore, the difference in their clinical effects may depend on their different target sites of action.