The N-methyl-D-aspartate receptor antagonist ketamine can elicit rapid and sustained antidepressant
effects in treatment-resistant patients with major depressive disorder. However, the
precise molecular mechanisms underlying ketamine’s antidepressant actions are currently
unknown. Recently, Williams et al. (
1
) demonstrated the role of the opioid system in the rapid antidepressant effects of
ketamine in patients with treatment-resistant major depressive disorder. In the small-sample,
single-center crossover trial, the authors investigated the effects of pretreatment
with the opioid receptor antagonist naltrexone (50 mg, 45 minutes before) on the antidepressant
effects of ketamine (0.5 mg/kg, intravenous) in the patients. In ketamine-responsive
patients with treatment-resistant depression, pretreatment with naltrexone profoundly
attenuated ketamine’s antidepressant effects, with none of the ketamine responders
meeting the response criterion at day 1. Furthermore, there were no differences in
ketamine-induced dissociation between two conditions. The authors conclude that opioid
receptor activation is required for ketamine’s acute antidepressant effects, although
the dissociative effects of ketamine are not mediated by the opioid system (
1
). However, the sample size (n = 7) of ketamine-responsive patients is too small. In addition, there are currently
no reports showing the role of opioid receptors in the antidepressant effects of ketamine
in rodent models of depression. Therefore, the present study was undertaken to examine
whether naltrexone can block the antidepressant effects of ketamine in chronic social
defeat stress (CSDS) and lipopolysaccharide (LPS)-treated inflammation models of depression.To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 10, 2018
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© 2018 Society of Biological Psychiatry.
