Aggressive behavior puts individuals at high risk for a variety of antisocial behaviors, including substance abuse and/or other criminal behavior. As a result, it is important to investigate some of the basic behavioral and pharmacological mechanisms which may affect and regulate aggressive behavior. For the past twenty years our laboratory has been engaged in the study of human aggressive responding under controlled conditions. We have developed a laboratory procedure, the Point Subtraction Aggression Paradigm (PSAP), which is now used in several laboratories in and outside the U.S. This phase our our research is looking at gamma aminobutyric acid (GABA) medications as potential interventions to decrease aggression as a venue which may influence future studies of pharmacotherapy of substance abuse. Determinations of acute drug administration will be conducted initially. If acute effects indicate relative selective suppression of aggressive responding, then chronic drug administration studies will be initiated. This continuation proposal will evaluate the acute and chronic effects of three GABAergic medications: baclofen, tiagabine and topiramate. Baclofen, an antispastic agent and a GABA-B agonist. Tiagabine, an anticonvulsant, is a selective GABA uptake inhibitor. Topiramate,an anticonvulsant, has a GABAergic effects involving different mechanisms. Based upon the broad range of possible clinical therapeutic targets for baclofen, tiagabine, and topiramate, we propose that the commonality for this pharmacological action is an effect upon impulse control disorders. Since aggression is not a recognized disorder, direct evaluation of these medications on aggressive behavior has not occurred. Clinical studies, although many are case reports and/or not well controlled, suggest possible usefulness in the following disorders: bulimia, binge eating, posttraumatic stress disorder, anxiety, mood disorders and the treatment of alcohol and substance abuse and dependence. Some of these disorders can in some instances be considered impulse disorders (alcoholism, substance abuse, bulimia and binge eating), while others may not have a clear association with impulse disorders but may be risk factor for such disorders, GABA as a major, if not the major, inhibitory system in the CNS, can be considered as an appropriate focus for pharmacological studies of impulse problem areas such as human aggression. The results of such studies may guide and supplement future clinical studies aimed at the suppression of human aggression, which may in turn impact other impulse problem behaviors.
Showing the most recent 10 out of 47 publications
