Arousal and Aggression

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.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…