Role of the medial prefrontal cortex in the effects of rapid acting antidepressants on decision-making biases in rodents
bioRxiv (Cold Spring Harbor Laboratory) January 23, 2020 Ca Hales, Jm Bartlett, R Arban et al. preprint
Ketamine and other rapid-acting antidepressants (RAADs) like CP-101,606 and scopolamine produce a positive bias in decision-making in rodents, shifting choices toward more optimistic outcomes. This effect is localized to the medial prefrontal cortex (mPFC), as targeted infusions into this brain region replicate the bias. In contrast, other NMDA receptor antagonists that lack rapid antidepressant effects do not induce this positive bias. Temporary inactivation of the mPFC with muscimol caused general behavioral disruptions rather than the specific positive bias seen with RAADs. These findings suggest that ketamine and similar RAADs act through a distinct mechanism involving the mPFC to alter affective biases, which may underlie their therapeutic action in major depressive disorder.