cAMP-dependent protein kinase signaling is required for (<i>2R,6R</i>)-hydroxynorketamine to potentiate hippocampal glutamatergic transmission
Lace M. Riggs, Edna F. R. Pereira, Scott M. Thompson, Todd D. Gould
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.
Topics & Concepts
Long-term potentiationExcitatory postsynaptic potentialSchaffer collateralNeurotransmissionGlutamatergicNeuroscienceNMDA receptorSynaptic plasticityPostsynaptic potentialGlutamate receptorProtein kinase AHippocampal formationChemistryBiologyReceptorKinaseCell biologyInhibitory postsynaptic potentialBiochemistryNeuroscience and Neuropharmacology ResearchTreatment of Major DepressionAnesthesia and Neurotoxicity Research