Subanaesthetic ketamine suppresses locus coeruleus mediated alertness effects - a 7T fMRI study.

BACKGROUND: The NMDA antagonist s-ketamine is gaining increasing use as a rapid-acting antidepressant, although its exact mechanisms of action are still unknown. In this study, we investigated ketamine in respect to its properties towards central noradrenergic mechanisms and how they influence alertness behavior.

METHODS: We investigated the influence of s-ketamine on the locus coeruleus (LC) brain network in a placebo controlled, cross-over, 7T functional, pharma- cological MRI study in thirty-five healthy male participants (25.1±4.2 years) in conjunction with the attention network task, to measure LC-related alert- ness behavioral changes.

RESULTS: We could show that acute disruption of the LC alertness network to the thalamus by ketamine is related to a behavioral alertness reduction.

CONCLUSION: The results shed new light on the neural correlates of ketamine beyond the glutamatergic system and underpin a new concept of how it may unfold its antidepressant effects.