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Chilled-out mice hold key to new treatments for psychological disorders


June 19, 2012

Researchers have found to block pathological aggression in mice that could lead to new treatments for variety of common psychological disorders in humans (Photo: Shutterstock)

Researchers have found to block pathological aggression in mice that could lead to new treatments for variety of common psychological disorders in humans (Photo: Shutterstock)

“Don’t make me angry. You wouldn’t like me when I’m angry,” the Hulk’s alter ego Bruce Banner famously said. Now researchers have made a discovery that might one day have implications for anyone considering Bruce as a potential house guest. The researchers have identified a brain receptor that malfunctions in overly hostile mice - a receptor that also exists in humans - and found a way to shut it down, offering the potential for the development of treatments for severe aggression.

The breakthrough by Marco Bortolato and Jean Shih from the University of Southern California’s (USC) School of Pharmacy, working with colleagues in Italy, builds on previous work by Bortolato and Shih, in which they identified a specific gene disposition resulting in low levels of the enzyme monoamine oxidase A (MAO A). They found that humans and mice with this congenital deficiency of the enzyme respond to stress with violent outbursts.

“The same type of mutation that we study in mice is associated with criminal, very violent behavior in humans,” Bortolato said. “But we really didn’t understand why that it is.”

To replicate elements of human pathological aggression in mice, the researchers combined low enzyme levels with stressful events early in life, such as trauma and childhood neglect.

“Low levels of MAO A are one basis of the predisposition to aggression in humans. The other is an encounter with maltreatment, and the combination of the two factors appears to be deadly: It results consistently in violence in adults,” Bortolato said.

Their research showed that extremely aggressive rodents lacking in MAO A required high levels of electrical stimulus to activate a specific brain receptor in the pre-frontal cortex known as NMDA. They add that, even when NMDA does work, it remains active for only a short period of time. Bortolato says that NMDA is thought to play a key role in helping people make sense of multiple, coinciding streams of sensory information.

“The fact that blocking this receptor moderates aggression is why this discovery has so much potential. It may have important applications in therapy,” Bortolato says. “Whatever the ways environment can persistently affect behavior – and even personality over the long term – behavior is ultimately supported by biological mechanisms.”

With pathological aggression a component in a number of common psychological disorders, including Alzheimer’s disease, autism, bipolar disorder and schizophrenia, the researchers are now studying the potential side effects of drugs that reduce the activity of the aggression receptor.

“Aggressive behaviors have a profound socioeconomic impact, yet current strategies to reduce these staggering behaviors are extremely unsatisfactory,” Bortolato said. “Our challenge now is to understand what pharmacological tools and what therapeutic regimens should be administered to stabilize the deficits of this receptor. If we can manage that, this could truly be an important finding.”

Source: USC

About the Author
Darren Quick Darren's love of technology started in primary school with a Nintendo Game & Watch Donkey Kong (still functioning) and a Commodore VIC 20 computer (not still functioning). In high school he upgraded to a 286 PC, and he's been following Moore's law ever since. This love of technology continued through a number of university courses and crappy jobs until 2008, when his interests found a home at Gizmag. All articles by Darren Quick

instead of shutting down the malfunctioning receptor (and affecting brain functions?), why not replenish in the deficient enzyme?!

Hala Chaoui

I agree, Hala, I can't understand why that's not even mentioned.

Harriet Russell

Stanislaw Lem "Return from the stars". People (and even some predator animals) are "betrizated" to make them non-violent.

That book was published in 1961.

How much of a step from giving this to violent criminals to making it mandatory for everyone?

Gregg Eshelman

Sounds a lot like the "reprogramming" in Clockwork Orange. So eventually this will be a shot or an implant that all of society will have to take. I can see them, testing it out in prisons systems first then becoming a court ordered "treatment if anyone looses their temper, or voices a strongly expressed opinion. Score another victory for Big Brother. With drones in the sky, OnStar's new retinal scanners billboards that can watch people and this, we have little to no hope left of becoming sheep on someone's farm.....


What doesn't pass the sniff test is the idea that low MAO connects closely to aggression. We prescribe MAO inhibitors frequently, and reports of systematic hikes in measures of aggression, anger, 911 calls have not been reported.

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