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

Nature neuroscience 2005 Sep 1; 8(9):1139-41

Link to PubMed abstract

Makara J JK, Mor M M, Fegley D D, Szabó S SI, Kathuria S S, Astarita G G, Duranti A A, Tontini A A, Tarzia G G, Rivara S S, Freund T TF, Piomelli D D

Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 8. Szigony u. 43., Budapest, H-1083 Hungary.

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.