Sex-dependent Effects of Formalin and Restraint on C-Fos Expression in the Septum and Hippocampus of the Rat

In the present study we have demonstrated that the same aversive stimulus induces different patterns of expression of transcription factors in the hippocampus and septum of male and female rats. We have investigated by immunohistochemistry the effects of a persistent painful stimulus and restraint stress on c-Fos expression in the hippocampus and septum of male and female rats. Subjects were randomly assigned to one of three experimental groups: (i) untreated controls, (ii) subcutaneous injection with formalin (50 microliters, 10%) in the right hindpaw, or (iii) immobilization in an adjustable restrainer. Formalin-treated and restrained animals were killed 90 min after the beginning of treatment. In both male and female rats, unilateral injection of formalin induced bilateral c-Fos expression in the hippocampus, but the number of labeled neurons was two-fold higher in females than in males. Restraint stress was not effective in c-Fos induction in the hippocampus of both sexes. In the septum, both treatments increased c-Fos, but this increase tended to be greater in males than females. Previous experiments have consistently shown that male and female rats react differently to aversive stimulation. The present findings suggest that hormonal and behavioral differences between the sexes are accompanied by genetic modifications in those brain areas involved in cognition and emotion.