Long-term social isolation can lead to overproduction of a chemical in the brain that causes increased aggression, stress and fear, a study has found.
Chronic social isolation has debilitating effects on mental health in mammals - for example, it is often associated with depression and post-traumatic stress disorder in humans.
Researchers at California Institute of Technology in the US have discovered that social isolation causes the build-up of a particular chemical in the brain, and that blocking this chemical eliminates the negative effects of isolation.
The work, published in the journal Cell, has potential applications for treating mental health disorders in humans, they said.
The researchers showed that prolonged social isolation leads to a broad array of behavioural changes in mice.
These include increased aggressiveness towards unfamiliar mice, persistent fear, and hypersensitivity to threatening stimuli.
For example, when encountering a threatening stimulus, mice that have been socially isolated remain frozen in place long after the threat has passed, whereas normal mice stop freezing soon after the threat is removed.
These effects are seen when mice are subjected to two weeks of social isolation, but not to short-term social isolation - 24 hours - suggesting that the observed changes in aggression and fear responses require chronic isolation.
In a previous study of the Drosophila fly, the lab of David J Anderson, a professor from Howard Hughes Medical Institute in the US, discovered that a particular neurochemical called tachykinin plays a role in promoting aggression in socially isolated flies.
To investigate whether the role of tachykinin in controlling social isolation-induced aggression might be evolutionarily conserved from insects to mammals, the team turned to laboratory mice.
The tachykinin gene Tac2 encodes a neuropeptide called neurokinin B (NkB).
Tac2/NkB is produced by neurons in specific regions of the mouse brain such as the amygdala and hypothalamus, which are involved in emotional and social behaviour.
The researchers found that chronic isolation leads to an increase in Tac2 gene expression and the production of NkB throughout the brain.
However, administration of a drug that chemically blocks NkB-specific receptors enabled the stressed mice to behave normally, eliminating the negative effects of social isolation.
Conversely, artificially increasing Tac2 levels and activating the corresponding neurons in normal, unstressed animals led them to behave like the stressed, isolated animals, researchers said....