Occlusion of dopamine-dependent synaptic plasticity in the prefrontal cortex mediates the expression of depressive-like behavior and is modulated by ketamine
Scientific Reports June 30, 2022 J. Lamanna, Francesco Isotti, Mattia Ferro et al.
In rats, vulnerability to chronic mild stress (CMS) is linked to a loss of dopamine-dependent synaptic plasticity in the medial prefrontal cortex (mPFC), likely due to altered AMPA receptor expression. This deficit is not present when rats receive a sub-anesthetic dose of ketamine, which may recruit dopaminergic areas like the ventral tegmental area. Chronic stress also shifts synaptic drive from the infralimbic and prelimbic subregions of the mPFC toward the basolateral amygdala, an effect that ketamine counteracts. These findings clarify neurophysiological mechanisms underlying stress vulnerability and ketamine's antidepressant action.