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

@article{Makara2005SelectiveIO,
  title={Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus},
  author={J. Makara and M. Mor and D. Fegley and S. I. Szab{\'o} and S. Kathuria and G. Astarita and A. Duranti and A. Tontini and G. Tarzia and S. Rivara and T. Freund and D. Piomelli},
  journal={Nature Neuroscience},
  year={2005},
  volume={8},
  pages={1139-1141}
}
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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