Reduction of serotonergic gene expression in the raphe nuclei of the midbrain under positive fighting experience in male mice

Abstract

The concept of a major inhibitory role of serotonin in aggressive behavior is widely accepted by investigators. There was ample evidence that a pharmacologically-induced increase in the serotonin activity attenuates agonistic behavior in animals, and that the manipulations inhibiting the brain serotonergic system can elicit aggressiveness in male mice and rats. Repeated experience of aggression in daily agonistic interactions has been shown to reduce serotonin activity in brain of victorious male mice. The study aimed to analyze expression of the serotonergic genes - Tph 2, Sert , Maoa and Htr 1 a , as well as the Bdnf and Creb genes in the midbrain raphe nuclei of male mice with positive fighting experience in daily encounters and male mice with the same track record of aggression followed by two-week no-fight period. It has been shown that mRNA levels of the serotonergic and Creb genes are reduced in the winners in comparison with male mice without consecutive positive fighting experience of aggression. After the fighting deprivation the Tph 2, Sert , Bdnf and Creb genes recover their expression while mRNA levels of the Maoa and Htr 1 a genes proceed at a significantly higher level as compared with the respective controls. Downregulation of serotonergic genes is indicative of the inhibition of serotonergic activity under repeated experience of aggression. Nevertheless recovering of Tph 2 and Sert gene expression and overexpression of the Maoa and Htr 1 a genes after no-fight period suggest that changes in brain serotonergic activity are not main cause of the behavioral pathology developing in male mice in this experimental context.