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Several studies in humans indicate that a single dose of ketamine, an antagonist of the N-methyl-d-aspartate (NMDA) receptor, can produce rapid, temporary improvement of refractory major depression. Researchers investigated potential mechanisms of these effects in a series of experiments using rats exposed to mild, chronic (21 days), unpredictable stress (e.g., tilted cages, crowded housing, isolation), which reliably produces rodent models of depressive behavior.
In these rats, researchers found indications of anhedonia (preference for water over sucrose after water deprivation) and anxiety (decreased feeding in a novel environment after food deprivation). Levels of synaptic proteins, density of apical spines, and excitatory postsynaptic cu…