Understanding the biological basis of violent outbursts in mice could lead to treatments for antisocial and aggressive behavior
Pathological rage can be blocked in mice, researchers have found, suggesting potential new treatments for severe aggression, a widespread trait characterized by sudden violence, explosive outbursts and hostile overreactions to stress.
In a study appearing today in the Journal of Neuroscience, researchers from the University of Southern California and Italy identify a critical neurological factor in aggression: a brain receptor that malfunctions in overly hostile mice. When the researchers shut down the brain receptor, which also exists in humans, the excess aggression completely disappeared.
The findings are a significant breakthrough in developing drug targets for pathological aggression, a component in many common psychological disorders including Alzheimer's disease, autism, bipolar disorder and schizophrenia.
"From a clinical and social point of view, reactive aggression is absolutely a major problem," said Marco Bortolato, lead author of the study and research assistant professor of pharmacology and pharmaceutical sciences at the USC School of Pharmacy. "We want to find the tools that might reduce impulsive violence."
A large body of independent research, including past work by Bortolato and senior author Jean Shih, USC University Professor and Boyd & Elsie Welin Professor in Pharmacology and Pharmaceutical Sciences at USC, has identified a specific genetic predisposition to pathological aggression: low levels of the enzyme monoamine oxidase A (MAO A). Both male humans and mice with congenital deficiency of the enzyme respond violently in response to stress.
"The same type of mutation that we study in mice is associated with criminal, very violent behavior in humans. But we really didn't understand why that it is," Bortolato said.
Bortolato and Shih worked backwards to replicate elements of human pathological aggression in mice, including not just low enzyme levels but also the interaction of genetics with early stressful events such as trauma and neglect during childhood.