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Brief Communication

Nature Neuroscience 8, 1139–1141 (1 September 2005) | doi:10.1038/nn1521

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

Judit K Makara , Marco Mor , Darren Fegley , Szil|[aacute]|rd I Szab|[oacute]| , Satish Kathuria , Giuseppe Astarita , Andrea Duranti , Andrea Tontini , Giorgio Tarzia , Silvia Rivara , Tam|[aacute]|s F Freund & Daniele Piomelli

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.