Abstract
Cannabinoid receptors play key roles in brain function, and cannabinoid effects in brain physiology and drug-related behavior are thought to be mediated by receptors present in neurons. Neuron-astrocyte communication relies on the expression by astrocytes of neurotransmitter receptors. Yet, the expression of cannabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication remain largely unknown. We show that hippocampal astrocytes express CB1 receptors that upon activation lead to phospholipase C-dependent Ca2+ mobilization from internal stores. These receptors are activated by endocannabinoids released by neurons, increasing astrocyte Ca2+ levels, which stimulate glutamate release that activates NMDA receptors in pyramidal neurons. These results demonstrate the existence of endocannabinoid-mediated neuron-astrocyte communication, revealing that astrocytes are targets of cannabinoids and might therefore participate in the physiology of cannabinoid-related addiction. They also reveal the existence of an endocannabinoid-glutamate signaling pathway where astrocytes serve as a bridge for nonsynaptic interneuronal communication.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Animals
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Animals, Newborn
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Astrocytes / drug effects
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Astrocytes / physiology*
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Astrocytes / radiation effects
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Calcium / metabolism
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Cannabinoid Receptor Modulators / pharmacology
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Cannabinoid Receptor Modulators / physiology*
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Cell Communication / physiology*
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Electric Stimulation / methods
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Endocannabinoids*
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Excitatory Amino Acid Antagonists / pharmacology
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Glial Fibrillary Acidic Protein / metabolism
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Glutamic Acid / metabolism
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Hippocampus / cytology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neurons / drug effects
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Neurons / physiology*
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Neurons / radiation effects
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Patch-Clamp Techniques
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Photolysis
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Piperidines / pharmacology
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Pyrazoles / pharmacology
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Receptor, Cannabinoid, CB1 / deficiency
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Receptor, Cannabinoid, CB1 / genetics
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Receptor, Cannabinoid, CB1 / metabolism
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Type C Phospholipases / pharmacology
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Valine / analogs & derivatives
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Valine / pharmacology
Substances
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Cannabinoid Receptor Modulators
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Endocannabinoids
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Excitatory Amino Acid Antagonists
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Glial Fibrillary Acidic Protein
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Piperidines
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Pyrazoles
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Receptor, Cannabinoid, CB1
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AM 251
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Glutamic Acid
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Egtazic Acid
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-amino-5-phosphopentanoic acid
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Type C Phospholipases
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Valine
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Calcium