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Stimulation of endocannabinoid formation in brain slice cultures through activation of group I metabotropic glutamate receptors

  • Author(s): Jung, KM
  • Mangieri, R
  • Stapleton, C
  • Kim, J
  • Fegley, D
  • Wallace, M
  • Mackie, K
  • Piomelli, D
  • et al.
Abstract

Activation of group I metabotropic glutamate (mGlu) receptors drives the endocannabinoid system to cause both shortand long-term changes of synaptic strength in the striatum, hippocampus, and other brain areas. Although there is strong electrophysiological evidence for a role of endocannabinoid release in mGlu receptor-dependent plasticity, the identity of the endocannabinoid transmitter mediating this phenomenon remains undefined. In this study, we show that activation of group I mGlu receptors triggers the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG), but not anandamide, in primary cultures of corticostriatal and hippocampal slices prepared from early postnatal rat brain. Pharmacological studies suggest that 2-AG biosynthesis is initiated by activation of mGlu5 receptors, is catalyzed by phospholipase C (PLC) and 1,2-diacylglycerol lipase (DGL) activities, and is dependent on intracellular Ca2+ions. Realtime polymerase chain reaction and immunostaining analyses indicate that DGL-β is the predominant DGL isoform expressed in corticostriatal and hippocampal slices and that this enzyme is highly expressed in striatal neurons, where it is colocalized with PLC-β1. The results suggest that 2-AG is a primary endocannabinoid mediator of mGlu receptor-dependent neuronal plasticity. Copyright © 2005 The American Society for Pharmacology and Experimental Therapeutics.

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