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Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus

  • Author(s): Makara, JK
  • Mor, M
  • Fegley, D
  • Szabó, SI
  • Kathuria, S
  • Astarita, G
  • Duranti, A
  • Tontini, A
  • Tarzia, G
  • Rivara, S
  • Freund, TF
  • Piomelli, D
  • et al.

Published Web Location

https://doi.org/10.1038/nn1521Creative Commons Attribution 4.0 International Public License
Abstract

The functions of 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid found in the brain, remain largely unknown. Here we show that two previously unknown inhibitors of monoacylglycerol lipase, a presynaptic enzyme that hydrolyzes 2-AG, increase 2-AG levels and enhance retrograde signaling from pyramidal neurons to GABAergic terminals in the hippocampus. These results establish a role for 2-AG in synaptic plasticity and point to monoacylglycerol lipase as a possible drug target. © 2005 Nature Publishing Group.

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