Pharmacological Aspects of NMDA Receptors, mGluR5, and Endocannabinoids

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Scopus citations


Current evidence indicates that metabotropic glutamate receptors (mGluRs) and N-methyl-. d-aspartate (NMDA) receptors interact with endocannabinoid (eCB) signaling. Synaptic depression is often mediated by eCBs serving as retrograde messengers at cannabinoid receptor 1 (CB1) and other cannabinoid receptors. Depolarization-induced suppression of inhibition (DSI) is a transient suppression of inhibitory synaptic transmission triggered by a depolarizing pulse. Dependency of DSI on mGluRs is variable among brain regions, but eCB production and CB1 activation on inhibitory terminals are essential for the temporary reduction of GABA release. In the hippocampus, high frequency stimulation induces long-term depression (LTD) in inhibitory neurons. In this LTD, glutamate release activates mGluRs, leading to eCB formation, and inhibition of GABA release via heteropresynaptic CB1. Similar mechanisms are thought to contribute to heterosynaptic and possibly homosynaptic LTD in excitatory neurons. Whereas exogenously administered cannabinoids disrupt long-term potentiation (LTP), a cellular model of memory and learning, eCBs may paradoxically augment LTP induction because eCBs can suppress inhibitory GABAergic interneurons, and GABAergic inhibition modulates excitatory LTP. While postsynaptic mGluR5 is likely important for eCB formation, the role of NMDARs is less certain. NMDAR activation may have additional actions, including adverse effects on CB1 signaling. Some of these NMDAR effects may involve activation of transient receptor potential vanilloid 1 (TRPV1).

Original languageEnglish
Title of host publicationHandbook of Cannabis and Related Pathologies
Subtitle of host publicationBiology, Pharmacology, Diagnosis, and Treatment
PublisherElsevier Inc.
Number of pages9
ISBN (Electronic)9780128008270
ISBN (Print)9780128007563
StatePublished - Jan 24 2017


  • CB1
  • GPR55
  • LTD
  • LTP
  • Retrograde messenger
  • TRPV1

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