Social animals, whether mice or men, become anxious when isolated from others. While this fact has long been known to researchers, and to even moderately keen lay observers, the mechanism that creates this anxiety has only recently become clear. A 2005 study from the University of Illinois at Chicago (UIC) reported that mice isolated for 4 weeks had reduced levels of allopregnanolone, a key modulator of the neurotransmitter GABA. GABA has many functions in the brain, though, so it was not clear at that time if allopregnanolone is the link between isolation and anxiety.

In November 2007, a team from UIC published the revealing results of a more thorough follow-up study in Proceedings of the National Academy of Sciences. By meticulously measuring the amount of allopregnanolone in hundreds of brain regions, researchers determined that while isolated mouse brains had slightly less than 50% of normal levels overall, the deficit was much higher in some areas than others. Significantly, the only large deficits were in connections to the amygdala, a region that regulates fear and aggression.

It is reasonable to infer a chain of causation from the location of deficits— isolation triggers a reduction in allopregnanolone, which impairs GABA specifically for the task of relaxation. The fact that this chain has been observed only in mice raises the perennial question of whether the furry favorite of the laboratory is sufficiently analogous to humans to draw accurate conclusions. While mice are obviously very different from us in many ways, a look at the work of Dr. Eric Nestler should reassure doubters that mouse studies can lead to valuable medications. Dr. Nestler socially isolated mice, causing depression symptoms that were then cleared up by a very popular human drug— Prozac.

It makes evolutionary sense for isolation to trigger a mechanism that hinders relaxation; social outcasts are often in extreme danger compared to those with access to support and cooperation. However, as with most negative emotions, humans can be unbalanced to the point that their quality of life suffers. While therapy can often alleviate feelings of isolation, allopregnanolone-based medicines may soon offer another lifeline.