Elevated levels of glutamate and serotonin may drive intense aggression

24 Apr

Increased levels of the neurotransmitters glutamate and serotonin are associated with intense aggression in male mice, finds a new study, suggesting a similar mechanism may also drive violence and psychopathy in human males.

Because of similarities in neurobiology, studying aggression in mice may lead to an enhanced understanding of antisocial, violent and psychopathic behavior in humans.

The study authors, from the Mouse Genomics Resource Laboratory in the National Institute of Genetics in Shizuoka, Japan, explain that males of many animal species have evolved aggressive behaviors to compete with other males for mates, food and shelter.

However, the authors say that when this “adaptive species-typical aggression” escalates into “intense aggression,” the behavior becomes destructive.

Because there are similarities in the neurobiology of aggression between rodents and humans, the researchers consider that studying aggression in mice may lead to an enhanced understanding of antisocial, violent and psychopathic behavior in humans.

Previous studies, in species ranging from invertebrates to humans, have found that serotonin – the hormone in the brain that produces “happiness” – is implicated in the control of aggression more than any other molecule.

In 2006, for instance, a study presented at the International Congress of Neuroendocrinology suggested that aggression in men may be influenced by variations in one of two genes involved in the activity of serotonin. However, the study also found that genetics were only predictive of aggression among men who reported more “cynical and hostile” attitudes toward others, or if they were the children of fathers who never completed high school.

A 2007 study found that genetically engineering fruit flies to produce elevated levels of serotonin also increased levels of aggression in those flies.

New study focused on the dorsal raphe nucleus – the brain’s serotonin hub

The National Institute of Genetics team focused its attention on a brain region known as the dorsal raphe nucleus (DRN) – located in the most primitive part of the brain – which houses the largest group of the brain’s serotonin-producing neurons.

The activity of the serotonin production in the DRN is regulated by several neurotransmitters, including glutamate, γ-aminobutyric acid (GABA) and serotonin itself. The authors note that some psychiatric disorders, such as anxiety, depression and aggression, have previously been linked to an imbalance between levels of glutamate and GABA.

The researchers used the standard laboratory experiment to measure aggression in mice – introducing an intruder mouse into a resident mouse’s territory and observing frequency and intensity of biting and threatening postures.

However, the team broke ground by implanting the brains of living mice with a probe that can both microinject drugs and collect brain fluid samples.

Using this novel in vivo microdialysis approach, the researchers were able to observe an increase in glutamate release in the DRN during moments of aggression between the mice. Levels of serotonin also increased in the DRN and the medial prefrontal cortex during intensely aggressive behavior, but not during “normal adaptive aggression.”

What the team concludes, therefore, is that glutamate input to the DRN is critical for escalating aggressive behavior and thus causes a surge of serotonin in the DRN.

The researchers hope that their findings, published in The Journal of Neuroscience, may suggest targets for future extreme antisocial behavior treatments.

Recently on Medical News Today, we looked at an opinion piece published in The BMJ by Prof. David Healy, who argued that the popular belief that low levels of serotonin cause depression is a myth, and that there has never been any correlation between potency of serotonin effect and treatment of depression.