In a related study, individual variations in the development of learned helplessness (see Supplementary information S1 (box)) among inbred mice were related to the expression of a transcription factor, FoSB, in the ventrolateral region of the periaqueductal grey (vlPAG) in the midbrain68. This brain area has long been associated with passive responses to stress69, which can predict vulnerability over resilience (see above). Berton et al.68 showed that the induction of FoSB in vlPAG neurons in resilient animals suppressed the expression of the neuropeptide substance P in these cells, which in turn reduced substance P transmission to target regions such as the nucleus accumbens and perhaps the amygdala. Inhibition of substance P in the nucleus accumbens specifically was then shown to be sufficient to mimic resilience. These observations suggest the use of substance P antagonists — that is, neurokinin 1 receptor antagonists — as a way to promote resilience in humans.
