Ketamine restores escape behavior by re-engaging dopamine systems to drive cortical spinogenesis
bioRxiv Preprint Server March 11, 2020 M Wu, S Minkowicz, V Dumrongprechachan et al. 3 citations preprint
Prolonged stress can lead to maladaptive learning, but the antidepressant ketamine can restore escape behavior in a learned helplessness paradigm. Dopamine neuron activity in the ventral tegmental area changes systematically during aversive learning and predicts future sensitivity to ketamine treatment. Ketamine's effects depend on dopamine signaling, as chemogenetic inhibition blocks them and optogenetic activation mimics them. In the medial prefrontal cortex, ketamine recovers dendritic spine formation on pyramidal neurons in a dopamine-dependent manner, reversing stress-induced reductions. These findings reveal circuits linking dopamine dynamics, aversive learning, and plasticity enhancements driven by ketamine.