Aggressive behavior puts individuals at high risk for a variety of antisocial behaviors in addition to substance abuse, and such aggressive behavior is a major component of the diagnostic criteria for childhood conduct disorder. Adolescents and adults with a history of childhood conduct disorder typically continue to engage in antisocial behavior in adulthood, and are at the highest risk for substance abuse and criminal activity. For the past twenty years, the investigator's laboratory has been engaged in the study of human aggressive responding under controlled conditions. They have developed a laboratory procedure, the Point Subtraction Aggression Paradigm (PSAP), which is now used in several laboratories in and outside the U.S. Since aggressive behavior is intimately involved in the risk for substance abuse, it is important to investigate some of the basic biological mechanisms that may regulate this behavior. Five GABA related drugs will be studied to determine their effects on aggressive behavior in two different populations of subjects: 1) Subjects with a history childhood conduct disorder (CD) + current antisocial personality disorder (ASPD), probably the highest risk population and; 2) Matched controls. The drugs to be employed are: baclofen a GABA B agonist, tiagabine a selective GABA reuptake inhibitor, lorazepam a GABA A agonist, flumazenil a specific GABA A antagonist and gabapentin a GABA releasing agent. The proposed research will provide information about the role of GABA in human aggression. Understanding the different biological factors involved in human aggression may lead to intervention/prevention strategies that will reduce the risk for substance dependence among high-risk populations.
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