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Open Access Publications from the University of California

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

  • Author(s): Makara, Judit K
  • Mor, Marco
  • Fegley, Darren
  • Szabó, Szilárd I
  • Kathuria, Satish
  • Astarita, Giuseppe
  • Duranti, Andrea
  • Tontini, Andrea
  • Tarzia, Giorgio
  • Rivara, Silvia
  • Freund, Tamás F
  • Piomelli, Daniele
  • et al.

Published Web Location Commons 'BY' version 4.0 license

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.

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