Lithium augmentation of ketamine increases insulin signaling and antidepressant-like active stress coping in a rodent model of treatment-resistant depression
Translational Psychiatry November 25, 2021 Blair J. Price, Brooke Morath, Mayo Clinic et al.
In a rodent model of antidepressant resistance, combining lithium with ketamine produced a robust antidepressant-like effect, as shown by reduced immobility and shorter latency to immobility in the forced swim test. The combination also increased blood levels of mTOR and insulin. In the prefrontal cortex, the treatment altered signaling proteins differently in two subregions: mTOR and Akt phosphorylation increased in the infralimbic area, while mTOR phosphorylation decreased in the prelimbic area. These findings suggest lithium may augment ketamine's effects in treatment-resistant conditions, linked to peripheral insulin and region-specific prefrontal signaling.