Arousal and Aggression

The Effects of Intranasal Vasopressin and Oxytocin on Arousal and Aggression
2006 Seed Grant
Royce J. Lee, M.D.
The University of Chicago

The ultimate goal of this work is to develop new treatments for pathological aggression based on a mechanistic understanding of its neurobiology. We know from extensive research in rodents and primates that the stress-related neurohormones vasopressin and oxytocin playa neurotransmitter-like role, and have specific facilitating and suppressing effects on aggression. It has recently been discovered that although vasopressin and oxytocin do not easily cross the blood brain barrier when administered orally or intravenously, they can cross into brain when administered intranasally via the olfactory nerve. Both hormones are available by prescription, and are safe to administer. This experiment will apply intranasal vasopressin and oxytocin to healthy volunteer subjects, in order to measure their effect, compared to placebo, on two phenomena: 1) brain electrical activity during an attentional task as measured by EEG and 2) behavioral aggression as measured by a competitive computer game against an imaginary opponent. Based on data from animal studies and from Dr. Lee’s laboratory, he believes that neurophysiologic arousal and aggression will be increased by vasopressin, and decreased by oxytocin. This study has been designed to gather preliminary data for a larger NIH proposal, and to provide an opportunity to acquire training in specialized EEG techniques.

Worldwide, aggression is one of the leading causes of death, suffering, social dysfunction, and public health care cost. As illustrated by a recent report of the World Health Organization on violence, in the United States alone, a single form of violence (shooting), in a single year cost the public an estimated $126 billion. Aggression that is caused by an underlying neuropsychiatric disorder may be amenable to biomedical treatment. There are currently no FDA.approved treatments of aggression or aggression related disorders (i.e. Intermittent Explosive Disorder). This partly reflects our lack of understanding of the underlying neurobiology of aggression in humans. This project will collect preliminary data for a long-term effort to study stress neuropeptide mechanisms of aggression in humans. The ultimate goal of the work is to develop safe, effective treatments of pathological aggression to reduce suffering, dysfunction, and public health expenditure.

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