Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function

J Psychopharmacol. 2021 Jun;35(6):652-667. doi: 10.1177/02698811211005627. Epub 2021 Apr 25.


Background: Sleep consolidates declarative memory by repeated replay linked to the cardinal oscillations of non-rapid eye movement (NonREM) sleep. However, there is so far little evidence of classical glutamatergic plasticity induced by this replay. Rather, we have previously reported that blocking N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors does not affect sleep-dependent consolidation of declarative memory.

Aims: The aim of this study was to investigate the role of metabotropic glutamate receptor 5 (mGluR5) in memory processing during sleep.

Methods: In two placebo-controlled within-subject crossover experiments with 20 healthy humans each, we used fenobam to block mGluR5 during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) in the evening, then received the drug and recall was tested the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II participants learned new word-pairs in the morning after sleep.

Results/outcomes: Surprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memory-relevant EEG oscillations. In NonREM sleep, fenobam suppressed 12-15 Hz spindles but augmented 2-4 Hz delta waves, whereas in rapid eye movement (REM) sleep it suppressed 4-8 Hz theta and 16-22 Hz beta waves. Notably, under fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation.

Conclusions/interpretations: Our findings indicate that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations.

Keywords: Sleep; consolidation; long-term memory; metabotropic glutamate receptors; oscillations.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography
  • Humans
  • Imidazoles / pharmacology*
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Receptor, Metabotropic Glutamate 5 / antagonists & inhibitors*
  • Receptor, Metabotropic Glutamate 5 / metabolism
  • Sleep / drug effects*
  • Sleep / physiology
  • Sleep, REM
  • Young Adult


  • GRM5 protein, human
  • Imidazoles
  • Receptor, Metabotropic Glutamate 5
  • fenobam