An interesting study looked at similarities and differences in the effects of two medications that have anti-depressant effects and yet are extremely different in terms of how they work: ketamine and imipramine (a tricyclic antidepressant).
This industry supported study looked at the effects of these two agents on a reward circuit (involving the prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala – see picture on the right) in the brain.
This circuit has been shown to be activated in substance use, and one theory about what causes substance use is the “hijacking” of these circuits so that they respond preferentially to ingestion of the triggering substance and do not respond to environmental cues and rewards. The circuits have been shown to be deactivated in depression – and this deactivation is linked to the loss of pleasure (anhedonia) and motivation associated with depressed mood.
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]. (http://dx.doi.org/10.1016/j.biopsych.2016.06.012)