Without BDNF in the circuit, an animal can't learn that a social stimulus is threatening and respond appropriately.

One of the cardinal features of addiction is how long-lived it is, ... A key question in the field has been: By what mechanisms do drugs of abuse cause changes in the brain that last this long?

Our study provides insight into how chronic stress triggers changes in the brain that are much more long-lived than the effects of existing antidepressants.

The challenge is to find a way to inhibit BDNF signaling within the reward pathway specifically. The many genes we show that are regulated by BDNF or antidepressants in this pathway may provide clues.

Removal of BDNF before bullying, or treatment with antidepressants after bullying, both removed the behavioral abnormality observed.

The social-defeat process induced production of BDNF in the reward circuit. Without BDNF in the circuit, an animal can't learn that a social stimulus is threatening and respond accordingly.