Any attempt to gain insight into the biological substrates of violence, which the National Center for Disease Control has labeled the most prominent health concern afflicting Americans, ought to address interactions of environmental and biological determinants, and do so in a way that suggests the generality of these mechanisms. Transient testosterone (T) surges that follow successful aggression are hypothesized to act as positive reinforcers and as rapid activators of aggression through actions on membrane steroid receptors. Exogenously administered T-surges, successful aggression in intact animals, and successful aggression in castrates with tonic-release T-implants will be tested for reinforcement properties in an operant conditioning paradigm. Measurement of aggressive responsiveness to intruding males shortly after administration of exogenous T-surges will be used to test rapid activating effects of T. Membrane binding sites for T and its metabolites, estradiol and 5 alpha-dihydrotestosterone, will be sought and characterized using conjugates of the steroids to bovine serum albumin and quantitative autoradiography of cryostat sections of the forebrain. If regions of high expression are found and binding sites have the characteristics of receptors, the cDNA corresponding to those sites will be cloned. Cloning will employ insertion into a plasmid vector, expression in eukaryotic host cells, and several rounds of expression screening and retransfection, before isolating and sequencing insert DNA. Understanding mechanisms of aggression in the study organism, Anolis carolinensis, will facilitate future comparative study using a subgroup of its over 250 congeners.
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