This effect has been termed defensive aggregation, and is facilitated by oxytocin (Bowen et al., 2012 and Bowen and McGregor, 2014). Exposure to chronic social defeat stress leads to social avoidance, altered fear acquisition and elimination, anhedonia, changes in neural circuitry and transmission, neurogenesis and metabolism in groups of exposed versus unexposed subjects (Chou et al., 2014 and Donahue et al., 2014). However, Pifithrin-�� chemical structure looking

at individual outcomes reveals a much more complex picture, even in inbred mice. For example, measuring social motivation after exposure to social defeat stress reveals a bimodal segregation of the group into affected and unaffected individuals. Affected individuals spend less time interacting with conspecific peers in the social zone, while unaffected (unsusceptible) individuals spend time in the social zone similar to unstressed individuals. Susceptibility

to social aversion following social defeat is associated with a suite of other signs of stress including decreased sucrose preference, decreased body weight, and increased sensitivity to cocaine-induced conditioned place preference (Krishnan et al., 2007). What is the difference between responders and non-responders, or a resilient vs. vulnerable trajectory? Interestingly, this resilience phenotype did not correlate with social motivation pre-stress, nor with levels of circulating glucocorticoids (Krishnan et al., 2007). However, stress-susceptibility has been correlated with stress-induced CP-673451 cost increase in levels of brain derived neurotrophic factor (BDNF), a key regulator of dopamine release in the nucleus accumbens (NAc). Following 10 days of repeated social defeat, BDNF protein levels were persistently elevated in the NAc of mice. Reduction of BDNF levels Carnitine dehydrogenase in the ventral tegmental area (VTA) via local BDNF knockdown provided an antidepressant-like effect relative to untreated, defeated mice and

prevented social aversion (Berton et al., 2006). Investigation of the individual differences between susceptible and unsusceptible mice revealed that susceptibility was characterized by increased NAc BDNF, but reinforced the importance of BDNF release from the VTA, as knockdown in the VTA but not NAc promoted resilience. Susceptibility to defeat was further shown to be mediated by enhanced firing of VTA dopamine neurons, with resilience characterized by a lack of activity-dependent BDNF release (Krishnan et al., 2007). Interestingly, unsusceptible individuals were not lacking a neural response, but in fact showed greater change in gene expression patterns in the VTA than susceptible individuals – suggesting that behavioral non-responsiveness is an active process and not merely a lack of the pathological process.