Although some people actively seek social isolation, there is abundant evidence that long periods alone cause depression and a variety of negative physical health effects in people. There is a reason solitary confinement is a punishment beyond ordinary prison. The brain molecule responsible for these effects may have been identified, along with a potential antidote.

Mice are even more social animals than humans, and when kept apart from others of their species become more reactive to negative stimulation. Famously, ignoring the same forces in rats led science to some deeply inaccurate conclusions about the effects of drugs, with devastating policy-making consequences.

Professor David Anderson of the California Institute of Technology and team isolated mice for two weeks and observed the anticipated increased aggression and negative reactions to stimuli, including persistent freeze responses even after danger has passed. This can be so bad that it becomes unsafe to return mice to collective accommodation lest they attack the others. They found an increase in tachykinin 2/neurokinin B peptide, or Tac2/NkB, which they believe is the chemical in the brain responsible for the isolated animals' stronger reactions.

Mice, including these harvest mice, are happiest together. We've found a molecule over-produced when they are isolated, which causes many of the negative effects, as well as a drug that counteracts this. Captivelight/Shutterstock

"We discovered that Tac2/NkB is upregulated broadly throughout the mouse brain in multiple brain regions that are involved in different types of emotional coping behaviors and aggression," Anderson said in a statement.

Rather than a single master switch boosting Tac2/NkB, with flow-on effects as the signaling molecule spread through the brain, it appeared that each sensitive region overproduced Tac2/Nkb when deprived of company, with behavioral effects relevant to that region.

When Anderson injected isolated mice with osanetant, a neurokinin receptor antagonist, he found they behaved more like those kept with their peers. Naturally, we can't ask the mice if the osanetant reduces loneliness, but their behavior indicated they were at least not experiencing the effects of social isolation in the usual way, and could comfortably be rehoused with other mice.

In contrast, Anderson reports in Cell he and co-authors induced over-production of Tac2/NkB in group-housed mice. "When we did that, we can mimic many of the effects of social isolation," Anderson said.

The work follows on from a similar study Anderson conducted on Tak2 and aggression in isolated fruit flies. The authors think any brain mechanism that unites a mammal with an insect is likely to have been preserved in humans, particularly, as co-author Dr Moriel Zelikowsky pointed out, “Humans have an analogous Tac2 signaling system.”

Osanetant has already been found to be safe for humans during unsuccessful attempts to use it to treat psychosis, and might prove effective at countering the well-established negative health effects of social isolation. The potential benefits are large and obvious, but raise difficult questions about whether a pill can ever be a true substitute for social connection, and if we want to treat the symptoms, not the cause.