cAMP-dependent protein kinase signaling is required for (<i>2R,6R</i>)-hydroxynorketamine to potentiate hippocampal glutamatergic transmission-Reference-Cited by-同舟云学术

cAMP-dependent protein kinase signaling is required for (2R,6R)-hydroxynorketamine to potentiate hippocampal glutamatergic transmission

Published:2024-01-01 Issue:1 Volume:131 Page:64-74
ISSN:0022-3077
Container-title:Journal of Neurophysiology
language:en
Short-container-title:Journal of Neurophysiology

Author:

Riggs Lace M.¹²,Pereira Edna F. R.³⁴^ORCID,Thompson Scott M.²⁵,Gould Todd D.²³⁶⁷^ORCID

Affiliation:

1. Program in Neuroscience and Training Program in Integrative Membrane Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States

2. Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, United States

3. Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland, United States

4. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, United States

5. Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States

6. Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, United States

7. Veterans Affairs Maryland Health Care System, Baltimore, Maryland, United States

Abstract

Ketamine is a rapid-acting antidepressant and its preclinical effects are mimicked by its ( 2R,6R)-(HNK) metabolite. We found that ( 2R,6R)-HNK initiates acute adaptations in fast excitatory synaptic transmission by potentiating glutamate release via cAMP-PKA signaling at hippocampal Schaffer collateral synapses. This cAMP-PKA-dependent potentiation was not dependent on TrkB activation by BDNF, which functionally delimits the rapid synaptic effects of ( 2R,6R)-HNK from its sustained BDNF-dependent actions that are thought to maintain antidepressant action in vivo.

Funder

HHS | NIH | National Institute of General Medical Sciences

HHS | NIH | National Institute of Mental Health

U.S. Department of Veterans Affairs

Publisher

American Physiological Society

Subject

Physiology,General Neuroscience

Link

https://journals.physiology.org/doi/pdf/10.1152/jn.00326.2023

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