The focus of this research will be important neurobiological substrates of aggressive behavior in mice, and how genetic, developmental, and experiential determinants of aggression are mediated by specific neuronal systems. To study this problem systematically, an integrated multidisciplinary approach will be used to examine the behavior and neurobiology of lines of mice, derived from ICR foundational stock, which have been selected over 21 generations for high and low levels of aggression. Alterations in aggression induced by genetic, ontogenetic, and experiential factors will be related to specific neurobiological mechanisms. Preliminary data support the hypothesis that an important mechanism for genetically-induced behavioral differences is an alteration in dopaminergic activity in specific terminal regions. Thus, the aims of the proposed studies are: (1) To determine whether alterations in brain monoamine, particularly dopamine, activity in specific terminal regions mediate behavioral differences observed in mice selectively bred for high and low levels of aggression; (2) to determine whether developmental and genetic differences in aggression are due to alterations in the magnitude or temporal development of innervation of discrete catecholamine terminal fields; (3) to determine whether social experience alters the neurobiological mechanisms mediating genetic and developmental differences in aggressive behavior. Because there are qualitative and quantitative changes in aggressive behavior changes as a function of developmental period, and as a function of social experience, the activity of dopamine and other monoamine (serotonin and norepinephrine) systems in both high and low aggressive mice will be studied during ontogeny, using behavioral, pharmacological, neurochemical, receptor, and immunocytochemical techniques. A cosibial longitudinal design will be used that allows genetic, developmental, and experiential factors to be disentangled. Computer-supported observational methods (interactional analyses) will be used to quantify behavior, while high performance liquid chromatography (HPLC) and quantitative receptor autoradiography will be used to measure neurochemical and receptor changes in monoamine systems. Immunocytochemical techniques, using antisera to tyrosine hydroxylase (TH) and dopamine-beta-- hydroxylase (DBH), will be used to characterize the distribution of catecholaminergic fibers in specific brain regions of high and low aggressive mice. The proposed studies will provide important, new information about the neurobiology of aggression and timidity, and the brain mechanisms that mediate genetic, developmental, and experiential effects on social behavior.
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| Petitto, J M; Lysle, D T; Gariepy, J L et al. (1993) Genetic differences in social behavior: relation to natural killer cell function and susceptibility to tumor development. Neuropsychopharmacology 8:35-43 |
