Overview
Three research programs on the genetics of aggression in mice and one on that for humans concerned with effects of the 5-HT system, especially receptor subtypes, on aggression are presented in this symposium. For mice, inbred strains (Simon), transgenic strains (Hilakivi-Clarke), and knock-out strains (Brunner) have been used in studies of the offense type of aggression. Simon has shown that there is between strain polymorphism for steroid activation of aggression. These are androgen and estrogen sensitive pathways which appear to modulate serotonin function at 5HT1A and 5HT1B receptor sites. The strains used by Hilakivi-Clarke differ in the singe transgene (transforming growth factor alpha, TgfΞ±) This gene may affect aggression through multiple neurotransmitters systems, including dopamine, serotonin, and GABA, and these may involve the estrogen sensitive pathway as described by Simon. The strains used by Brunner differ in the gene for the 5HT1B receptor. One of the strains is a knock-out mutant of this gene. Aggressive behavior is facilitated in the knock-out as is ethanol consumption, cocaine self-administration, and motor but not cognitive impulsivity. These research programs illustrate some of the advantages and limitations of genetic approaches to investigating the neural and hormonal basis of aggression in mice. For humans (Goldman et al.), polymporhisms for tryptophan hydroxylase are associated with the risk of suicide and variants of the 5HT1B receptor are associated with antisocial alcoholism. Neither is associated with variants of the dopamine receptor, DRD2. In discussion, the relation of the animal to human research will be considered. For example, the research of Brunner and her colleagues on the 5HT1B receptor and aggression in mice was partially the basis for investigating the behavioral effects of polymorphisms of the 5HT1B receptor in humans by Goldman and his colleagues.