(2R,6R)-hydroxynorketamine exerts mGlu₂ receptor-dependent antidepressant actions.

ABSTRACT: Currently approved antidepressant drugs often take months to take full effect, and ∼30% of depressed patients remain treatment resistant. In contrast, ketamine, when administered as a single subanesthetic dose, exerts rapid and sustained antidepressant actions. Preclinical studies indicate that the ketamine metabolite (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] is a rapid-acting antidepressant drug candidate with limited dissociation properties and abuse potential. We assessed the role of group II metabotropic glutamate receptor subtypes 2 (mGlu₂) and 3 (mGlu₃) in the antidepressant-relevant actions of (2R,6R)-HNK using behavioral, genetic, and pharmacological approaches as well as cortical quantitative EEG (qEEG) measurements in

SUBMITTER: Zanos P 

PROVIDER: S-EPMC6442605 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature