Rodent ketamine depression-related research: Finding patterns in a literature of variability
Behavioural Brain Research August 13, 2019 Andrew J. Polis, Paul J. Fitzgerald, Pho J. Hale et al. 58 citations
Ketamine has rapid antidepressant effects in many people with major depression, a major finding in psychopharmacology. Rodent studies from the 1990s laid the groundwork, and subsequent research includes human and reverse translational animal experiments. While rodent literature generally agrees ketamine has rapid and sustained antidepressant-like effects, disagreements exist over its precise mechanism. This review summarizes variable findings on mechanism, and differences in effects by dose, species, strain, test, stressor, and experimenter sex. Previously unpublished mouse strain data suggest subanesthetic ketamine lacks robust antidepressant-like properties in unstressed animals and may promote depression-like behavior. The data best support ketamine acting via NMDA receptor antagonism, transiently boosting glutamatergic signaling. Future studies should address stress sensitivity to better model human depression.