Animal studies have greatly informed our understanding of the brain's reward circuitry and its possible importance for resilience. The best-established reward circuit is the mesolimbic dopamine system, which involves dopaminergic neurons of the VTA and their innervation of the nucleus accumbens and many other forebrain limbic regions (FIG. 3). VTA dopamine neurons can be viewed as gauges of reward: they are activated in response to a reward (for example, food, sex or social interaction) or even the expectation of a reward, and are inhibited by an aversive stimulus or the absence of an expected reward97. However, certain dopaminergic neurons are also activated by aversive stimuli, suggesting that they are more generally involved in mood regulation98. Indeed, an increasing number of studies report the involvement of the VTA–nucleus accumbens circuit in depression and antidepressant responses in humans and rodents, although there is not yet a clear consensus on the role of dopamine function per se in resilience and vulnerability. A recent study in the social-defeat paradigm in mice (see Supplementary information S1 (box)) has shown that increased activity of VTA dopamine
