(<i>R</i>)‐Ketamine exerts antidepressant actions partly via conversion to (<i>2R,6R</i>)‐hydroxynorketamine, while causing adverse effects at sub‐anaesthetic doses

Abstract

Metabolism of (R)-ketamine to (2R,6R)-HNK increases the potency of (R)-ketamine to exert antidepressant-relevant actions in mice. Adverse effects of (R)-ketamine require higher doses than those necessary for antidepressant-sensitive behavioural changes in mice. However, our data revealing that (R)-ketamine's adverse effects are elicited at sub-anaesthetic doses indicate a potential risk for sensory dissociation and abuse liability.