Steven Dubovsky, MD reviewing Bagot RC et al. Biol Psychiatry 2016 Jun 18.

Results from an animal study may yield new targets for more-effective medications.

Depression can disrupt neural circuits in depression. This industry-supported study used rodents to examine how two antidepressants with grossly different actions affect a neural reward circuit involving the prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. This circuit is involved in susceptibility, resistance, and antidepressant response to depressogenic circumstances. The test used here was social defeat stress (SDS), a validated animal model of depression.

Identically raised inbred mice were determined to be either susceptible or resilient to SDS (i.e., they did or did not exhibit social avoidance after exposure to threat from a dominant animal). After SDS, both acutely administered ketamine and chronically administered imipramine significantly reduced social avoidance, compared with saline, in about half of susceptible subjects. Among saline-treated animals, social avoidance was greater among susceptible mice than among resilient animals or control animals not previously exposed to SDS. Response to both treatments induced genes associated with resilience and down-regulated those associated with susceptibility. The pattern of response-associated changes in gene expression was similar for both drugs in the PFC, less so in other regions. Nonresponders to each medication had somewhat different patterns of gene expression in the nucleus accumbens and hippocampus.

CITATION(S):

Bagot RC et al. Ketamine and imipramine reverse transcriptional signatures of susceptibility and induce resilience-specific gene expression profiles. Biol Psychiatry 2016 Jun 18; [e-pub]. 

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