Cannabinoids activate p38 mitogen-activated protein kinases through CB1 receptors in hippocampus

J Neurochem. 2001 May;77(3):957-60. doi: 10.1046/j.1471-4159.2001.00333.x.


Cannabinoid receptors (CB1-R) are the target of a novel class of neuromodulators, the endocannabinoids. Yet, their signalling mechanisms in adult brain are poorly understood. We report that, in rat and mouse hippocampal slices, anandamide and 2-arachidonoylglycerol, synthetic cannabinoids, and delta(9)-tetrahydrocannabinol activated p38 mitogen-activated protein kinases (MAPK), but not c-Jun N-terminal kinase (JNK). In contrast, lysophosphatidic acid (LPA), a lipid messenger acting on different receptors, increased both p38-MAPK and JNK phosphorylation. The effects of cannabinoids on p38-MAPK were mediated through activation of CB1-R because they were blocked in the presence of SR 141716 A and absent in CB1-R knockout mice, two conditions that did not alter the effects of LPA. The activation of p38-MAPK by cannabinoids was insensitive to inhibitors of SRC: These results provide new insights into the cellular mechanisms by which cannabinoids exert their effects in hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabinoid Receptor Modulators
  • Cannabinoids / pharmacology*
  • Enzyme Activation / drug effects
  • Hippocampus / enzymology*
  • JNK Mitogen-Activated Protein Kinases*
  • Lysophospholipids / pharmacology
  • MAP Kinase Kinase 4
  • Male
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid
  • Receptors, Drug / deficiency
  • Receptors, Drug / genetics
  • Receptors, Drug / physiology*
  • p38 Mitogen-Activated Protein Kinases


  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Lysophospholipids
  • Receptors, Cannabinoid
  • Receptors, Drug
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases