CB₂ cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons.

Neuropharmacology
Brady K AtwoodKen Mackie

Abstract

The role of CB₂ in the central nervous system, particularly in neurons, has generated much controversy. Fueling the controversy are imperfect tools, which have made conclusive identification of CB₂ expressing neurons problematic. Imprecise localization of CB₂ has made it difficult to determine its function in neurons. Here we avoid the localization controversy and directly address the question if CB₂ can modulate neurotransmission. CB₂ was expressed in excitatory hippocampal autaptic neurons obtained from CB₁ null mice. Whole-cell patch clamp recordings were made from these neurons to determine the effects of CB₂ on short-term synaptic plasticity. CB₂ expression restored depolarization induced suppression of excitation to these neurons, which was lost following genetic ablation of CB₁. The endocannabinoid 2-arachidonylglycerol (2-AG) mimicked the effects of depolarization in CB₂ expressing neurons. Interestingly, ongoing basal production of 2-AG resulted in constitutive activation of CB₂, causing a tonic inhibition of neurotransmission that was relieved by the CB₂ antagonist AM630 or the diacylglycerol lipase inhibitor RHC80267. Through immunocytochemistry and analysis of spontaneous EPSCs, paired pulse ratios and coefficients ...Continue Reading

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Citations

Apr 8, 2014·Psychopharmacology·Ramy KhellaDaniel T Malone
Mar 29, 2014·Pflügers Archiv : European journal of physiology·Femke S den BoonTaco R Werkman
May 20, 2014·Expert Opinion on Investigational Drugs·Mellar P Davis
Sep 6, 2015·The International Journal of Neuropsychopharmacology·Marie FitzgibbonMichelle Roche
Oct 10, 2013·British Journal of Pharmacology·N MurataevaK Mackie
May 20, 2016·The Journal of Pharmacology and Experimental Therapeutics·Amey Dhopeshwarkar, Ken Mackie
May 10, 2013·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Ivana Hradilová SvízenskáPetr Dubový
Aug 12, 2014·Molecular Pharmacology·Amey Dhopeshwarkar, Ken Mackie
Sep 7, 2018·Frontiers in Cellular Neuroscience·Sumana GhoshVickram Ramkumar
Aug 20, 2019·Physiological Research·M ZubrzyckiM Zubrzycka
Feb 12, 2021·Journal of Neuroimmunology·Durga Shankar SharmaRavi Kumar Gutti
Feb 21, 2021·Progress in Neuro-psychopharmacology & Biological Psychiatry·Lucas Gomes-de-SouzaCarlos C Crestani
Jun 14, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gerwyn MorrisAndre F Carvalho

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