Reduced brain serotonin (5-HT) activity has been linked to impulsive and violent forms of aggression for decades. Despite a vast accumulation of data pertinent to the above observation, information about the possible mechanisms underlying such a decreased 5-HT functioning is virtually absent. Amongst many, reduced 5-HT biosynthetic capacity is a likely possibility in violent individuals and/or in high-aggressive animals. In order to examine this hypothesis, the current study principally aimed at the determination and comparison of the 5-HT biosynthetic capacity in three different strains of high- and low-aggressive mice obtained by artificial genetic selection. While low Tryptophan Hydroxylase (TPH) activity can be expected to lead to low 5-HT levels and pathological aggression, high TPH activity can be expected to increase 5-HT levels and normal territorial aggression. The above hypothesis was assessed by estimating the in-vivo synthesis rate and synthesis rate constant of 5-HT biochemically by measuring the accumulation of 5-hydroxytryptophan (5-HTP) following treatment with the central aromatic amino-acid decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015). Surprisingly, we found no differences in the 5-HT biosynthetic capacity between the high- and low-aggressive selection lines in their prefrontal cortices and raphe nuclei, two main brain regions closely involved in aggression control. Thus, the underlying inherent genetic differences in aggressiveness observed in these artificially selected mouse strains are not due to constitutive functional differences in their TPH activity in these brain regions. (C) 2009 Elsevier Inc. All rights reserved.