The abuse of androgenic-anabolic steroids (AAS) has increased dramatically amongst the adolescent population and represents a serious drug problem in the United States. The most consistently cited behavioral sequelae of AAS abuse is increased aggressive behavior. The arginine vasopressin (AVP) neural system has been strongly implicated in the regulation of aggressive behavior. It is hypothesized that abuse of anabolic steroids during the adolescent period of neural development results in increased aggressive behavior correlated with developmental changes in the AVP neural system. These changes may be a function of alterations in the expression of AVP and/or the expression and activity of specific AVP receptors. Alternatively, these developmental changes may be due to modifications in the synaptic connectivity of the AVP neural system. Studies outlined in this proposal will utilize an animal model to examine the behavioral and neurobiological effects of high dose AAS exposure during a period that is physiologically similar to adolescence in humans. The first set of experiments will determine whether exposure to AAS during adolescent development facilitates aggressive behavior in golden hamsters using the resident/intruder paradigm of offensive aggression. The next set of experiments will determine whether AAS exposure during adolescence alters the molecular biology and neurochemistry of the AVP neural system. These studies will employ the use of cDNA fragments, antibodies, and selective receptor ligands to visualize and quantitate the activity of the genes encoding AVP and the AVP V1A subtype receptor. The last set of experiments will determine whether exposure to AAS during adolescent development alters the synaptic connections of the AVP neural system. Changes in synaptic connectivity will be visualized and quantitated by wide-field digital microscopy and immunoelectron microscopy. The data obtained from these studies should provide valuable information regarding the increased risk of aggressive and violent behavior in those individuals who abuse AAS during early life, and the neurobiological sequelae of prolonged high dose use of AAS. This knowledge is important in helping us to identify developmental periods that are particularly vulnerable to environmental insult, and to document the neurobiological changes that may predispose individuals to behave in a self-destructive or violent manner later in life.
