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Genetics, 5-HT, and Aggression
Organizer: Stephen C. Maxson
University of Connecticut, Storrs, CT

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 research on the offense type of aggression.  For humans (Goldman et al.), polymporhisms for tryptophan hydroxylase are associated with the risk of suicide and variants of the 5HT1B receptor with antisocial alcoholism. 

Testosterone-serotonin interactions in aggression
Neal G. Simon
(Lehigh University, Bethlehem, PA)
Our understanding of the neurochemical and neuroendocrine systems regulating intermale aggression has progressed substantially over the past twenty years. Serotonin, via its action at 5HT1A and/or 5HT1B receptor sites, inhibits this behavior while testosterone is facilitative through androgen-sensitive or estrogen-sensitive pathways. Characterizing the interaction between these systems has been a recent objective. Biobehavioral, microinjection, and immunochemical studies have demonstrated that the major metabolites of testosterone differentially affect the ability of 5HT1A and 5HT1B agonists to decrease aggression. (back to top)

Transgenic TGF (mice and aggression)
Leena Hilakivi-Clarke
(Georgetown University, Washington, DC)
Transforming growth factor, a mediator of estrogen-regulated mitogenesis, plays an important role in the brain. We have found that transgenic male mice that overexpress TGF are highly aggressive. Castration reverses their increased aggressiveness. In addition, estradiol increases aggressive behavior in non-transgenic mice. Our data further indicate that serotonin turnover is significantly reduced in the brain stem of TGF mice. Since serotonin and estrogens interact with each other, both of them may be involved in controlling heightened aggression in the male TGF mice. (back to top)

Neurobiology of impulsive behavior in a serotonin 1B knockout mouse
Dani Brunner
(Hunter College CUNY and Columbia University, New York City, NY)
Impulsivity is important in drug addiction, violent aggression and violent suicide.  Using the serotonin 1B receptor knockout mouse we studied impulsivity in relation with serotonin in aggressive and appetitively motivated behavior. The impulsive characteristics of these mice are not due to change in cognitive functions: knockout mice have intact choice and timing capabilities and good discrimination of reward amounts. This mouse may prove an animal model of motor impulsivity. (back to top)

Genetic linkage of alcoholism and antisocial alcoholism
D. Goldman, J. Lappalainen, W.C. Knowler, R.L. Hanson, R. W. Robin, M. Urbanek, D. Guenther, E. Moore, P.H. Bennett, J. Long, M. Virkunnen, and M. Linnoila
(Laboratory of Neurogenetics, NIAAA, NIH, Rockville, MD)
Candidate gene and whole-genome linkage analyses on alcoholism and antisocial alcoholism were performed in population isolates: Finns among whom probands were alcoholic offenders and a large Southwestern American Indian family. Results included moderate-strong evidence for linkage at chromosome 11p [location of DRD4 dopamine receptor], 4p [GABAA cluster] and 4q [ADH cluster], sibpair linkage of antisocial alcoholism [alcoholism plus ASPD or intermittent explosive disorder] to the 5HT1B receptor gene previously implicated by mouse 5HT1B knockout studies. (back to top)