TABLE 3

Effects on synaptic glutamatergic transmission

Contained in this table are synaptic effects other than direct effects on NMDAR function, which are shown in Table 2. Studies and experiments that did not identify an effect are not summarized in this table; please refer to the text for these details.

Concentration/DoseTimingEffectSystemReferences
In vitro or ex vivo application
(2R,6R)-HNK
 0.3–30 µM (EC50 = 3.3 µM)1-h exposureIncreased fEPSP slopeaSC-CA1, rat hippocampal slicesRiggs et al. (2019)
 10 µM1-h exposureZanos et al. (2016)
 0.3–30 µM (IC50 = 3.8 µM)1-h exposureDecreased paired-pulse ratioRiggs et al. (2019)
 10 µM20-min exposureIncreased sEPSC frequency and amplitudeRat CA1 stratum radiatum interneuronsZanos et al. (2016)
 10 µM15- to 25-min exposureIncreased mEPSC frequency (no change in amplitude)Rat CA1 pyramidal neuronsRiggs et al. (2019)
 10 µM15-min exposureIncreased mEPSC frequency and amplitudeRat ventrolateral periaqueductal gray neuronsChou et al. (2018); Ye et al. (2019)
 10 µM1- to 17-min exposureNo change in AMPA-evoked currentsRat primary cortical neuronsShaffer et al. (2019)
 10 µM20-min exposureNo change in sEPSC frequency or amplitudeMouse CA1 interneurons
 3–30 µM (EC50 = 7.8 µM)2-h exposureNo change in baseline fEPSP SlopeSC-CA1, hippocampal slices from 14-day-old mouseKang et al. (2020)
Decreased LTP
(2S,6S)-HNK
 10 µM20-min exposureNo change in sEPSC frequency or amplitudeRat CA1 interneuronsZanos et al. (2016)
 10 µM1- to 17-min exposureNo change in AMPA-evoked currentsRat primary cortical neuronsShaffer et al. (2019)
 1–10 µM (EC50 = 1.0 µM)2-h exposureNo change in baseline fEPSP SlopeSC-CA1, hippocampal slices from 14-day-old mouseKang et al. (2020)
Decreased LTP
Racemic (2R,6R;2S,6S)-HNK
 20 µM30-min exposureNo change in fEPSP slopeSC-CA1, rat hippocampal slicesMichaelsson et al. (2019)
In vivo administration
 10 mg/kg, i.p.24 h post-treatmentIncreased glutamate releaseMouse prefrontal cortex, microdialysisPham et al. (2018)
 1 nmol/side bilateral intracortical infusion24 h post-treatment
 0.075 mg/kg, i.p.1 wk post-treatmentAttenuation of AMPAR-mediated EPSC burstsMouse hippocampal pyramidal neuronsChen et al. (2020)
 5 mg/kg, i.p.3.5 h or 1 day post-treatmentIncreased magnitude of and slowed decay of LTPSC-CA1, Wistar-Kyoto stress-susceptible rats, in vivo electrophysiologyAleksandrova et al. (2020)
 10 mg/kg, i.p.24 h post-treatmentReversed stress-induced increases in paired-pulse ratiosRat ventrolateral periaqueductal gray neuronsChou et al. (2018)
Reversed stress-induced decreased in inward AMPAR-mediated currents
Reversed stress-induced decreases in AMPA-evoked currents
Reversed stress-induced decreases in mEPSC frequency and amplitude
 10 mg/kg, i.p.24 h post-treatmentIncreased mEPSC frequency and amplitudeRat ventrolateral periaqueductal gray neuronsYe et al. (2019)
Decreased paired-pulse ratio
Increased stimulus response relationship
Increased AMPA-evoked currents
 10 mg/kg, i.p.24 h post-treatmentDecreased mEPSC frequency and amplitudeMouse dopaminergic ventral tegmental neuronsYao et al. (2018)
Decreased AMPAR:NDMAR ratio
No change in firing frequency
 10 mg/kg, i.p.24 h post-treatmentDecreased LTPMouse nucleus accumbens coreYao et al. (2018)
No change in stimulus response relation or paired-pulse ratio
 30 mg/kg, i.p.24 h post-treatmentIncreased serotonin and hypocretin-evoked sEPSC frequency and amplitudeMouse prefrontal cortex neuronsFukumoto et al. (2019)

  • SC-CA1, Schaffer collateral-CA1 hippocampal synapse; sEPSC, spontaneous excitatory postsynaptic current.

  • ↵a Shaffer et al. (2019) reported no change in SC-CA1 fEPSP slope after a 1-h exposure to 10 µM (2R,6R)-HNK.