The VTA-BLA-NAc circuit for sex reward inhibited by local GABA neurons under stress. Linshan Sun et al.
Anhedonia, inability to experience pleasure from rewarding or enjoyable activities, is the prominent symptom of depression that involves dysfunction of the reward processing system. Both genetic predisposition and life events are considered to increase the risk for depression, mainly life stress. The cellular mechanism underlying stress modulating the reward processing neural circuits and subsequently disrupting reward-related behaviors remains elusive. We identify the VTA-BLA-NAc pathway as being activated by sex reward. Blockade of the VTA-BLA-NAc circuit induces depressive-like behaviors, while reactivation of VTA neurons associated with sexual rewarding experience acutely ameliorates the impairment of reward-seeking behaviors induced by chronic restraint stress. Our histological and electrophysiological results show that the VTA neuron subpopulation responding to restraint stress inhibits the responsiveness of the VTA dopamine neurons to sexual reward. These results reveal the mechanism by which stress influence the brain reward processing system and provide a potential target for depression treatment.