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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003166-22
Application #
7633149
Study Section
Special Emphasis Panel (ZRG1-BBBP-C (02))
Program Officer
Wetherington, Cora Lee
Project Start
1984-09-01
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
22
Fiscal Year
2009
Total Cost
$245,879
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Alcorn 3rd, Joseph L; Green, Charles E; Schmitz, Joy et al. (2015) Effects of oxytocin on aggressive responding in healthy adult men. Behav Pharmacol 26:798-804
Alcorn 3rd, Joseph L; Rathnayaka, Nuvan; Swann, Alan C et al. (2015) Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder. Psychol Rec 65:691-703
Gowin, Joshua L; Green, Charles E; Alcorn 3rd, Joseph L et al. (2013) The role of cortisol and psychopathy in the cycle of violence. Psychopharmacology (Berl) 227:661-72
Alcorn 3rd, Joseph L; Gowin, Joshua L; Green, Charles E et al. (2013) Aggression, impulsivity, and psychopathic traits in combined antisocial personality disorder and substance use disorder. J Neuropsychiatry Clin Neurosci 25:229-32
Gowin, Joshua L; Green, Charles E; Alcorn, Joseph L et al. (2012) Chronic tiagabine administration and aggressive responding in individuals with a history of substance abuse and antisocial behavior. J Psychopharmacol 26:982-93
Lijffijt, Marijn; Cox, Blake; Acas, Michelle D et al. (2012) Differential relationships of impulsivity or antisocial symptoms on P50, N100, or P200 auditory sensory gating in controls and antisocial personality disorder. J Psychiatr Res 46:743-50
Gowin, Joshua L; Swann, Alan C; Moeller, F Gerard et al. (2010) Zolmitriptan and human aggression: interaction with alcohol. Psychopharmacology (Berl) 210:521-31
Lane, Scott D; Gowin, Joshua L; Green, Charles E et al. (2009) Acute topiramate differentially affects human aggressive responding at low vs. moderate doses in subjects with histories of substance abuse and antisocial behavior. Pharmacol Biochem Behav 92:357-62
Lieving, Lori M; Cherek, Don R; Lane, Scott D et al. (2008) Effects of acute tiagabine administration on aggressive responses of adult male parolees. J Psychopharmacol 22:144-52
Nouvion, Sylvain O; Cherek, Don R; Lane, Scott D et al. (2007) Human proactive aggression: association with personality disorders and psychopathy. Aggress Behav 33:552-62

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