From gene to aggressive behavior: the role of brain serotonin.

This article addresses a question at the juncture of neurophysiology and neurogenetics--the role of the brain neurotransmitter serotonin in the genetic control of behavior. Published data are presented, along with results obtained from studies performed at the Behavioral Neurogenomics Laboratory. The role of protein elements of the brain serotonin system (key enzymes in serotonin metabolism and serotonin 5-HT(1A) receptors), which are subject to the direct influence of genes, in the genetic predisposition to aggressive behavior is discussed. Experimental results obtained in Norwegian rats selected over more than 50 generations for the absence of aggressivity and for high aggressivity to humans are presented, along with data from experiments on mouse lines and mice with genetic knockout of MAO A. These data provide evidence that 1) brain serotonin makes a significant contribution to the mechanisms underlying genetically determined individual differences in aggressivity, and 2) the genes encoding the main enzymes of serotonin metabolism in the brain (tryptophan hydroxylase-1 and MAO A) and the 5-HT(1A) receptor are members of a set of genes modulating aggressive behavior.