Antidepressant-like effects of extinction learning as an animal model of behavioral therapy

Exposure-based behavioral therapy, the most effective treatment for posttraumatic stress disorder (PTSD), also reduces depressive symptoms. However, neurobiological mechanisms underlying the beneficial effects of exposure-based behavioral therapy on depression remain unknown. Our lab has established fear extinction as a rat model of exposure therapy to investigate the mechanisms underlying its therapeutic behavioral effects in chronically stressed rats. In this study, we demonstrated that extinction learning reduced immobility in the forced-swim test and reversed chronic stress-induced reduction in sucrose preference. Chemogenetic inactivation of pyramidal neurons in the ventral medial prefrontal cortex (vmPFC) prevented these antidepressant-like effects of extinction. Extinction learning enhanced synaptic plasticity, reflected by enhanced optogenetically-induced long-term potentiation of mPFC responses evoked by stimulation of the afferent input from the mediodorsal thalamus (MDT). These results suggest that activity-dependent neuroplasticity induced in vmPFC by extinction learning may contribute to its antidepressant-like effects after chronic stress.