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Opposite control of frontocortical 2‐arachidonoylglycerol turnover rate by cannabinoid type‐1 receptors located on glutamatergic neurons and on astrocytes
Author(s) -
Belluomo Ilaria,
Matias Isabelle,
Pernègre Camille,
Marsicano Giovanni,
Chaouloff Francis
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13044
Subject(s) - glutamatergic , endocannabinoid system , palmitoylethanolamide , receptor , forebrain , 2 arachidonoylglycerol , cannabinoid receptor , medicine , biology , endocrinology , cannabinoid , hippocampal formation , neuroscience , chemistry , glutamate receptor , biochemistry , central nervous system , agonist
This study examined the respective influences of cannabinoid type‐1 (CB 1 ) receptors expressed either in forebrain GABAergic neurons, in cortical glutamatergic neurons, or in astrocytes on the turnover rates of the endocannabinoids N ‐arachidonoylethanolamide (AEA) and 2‐arachidonoylglycerol (2‐AG), and the non‐cannabinoid N ‐acylethanolamides, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA), in mouse forebrain regions. To this end, conditional mutant mice lacking CB 1 receptors from either of these cell types were pre‐treated systemically with JZL195, a dual inhibitor of fatty acid amide hydrolase, the enzyme degrading AEA, PEA, and OEA, and of monoacylglycerol lipase, the main 2‐AG‐degrading enzyme. The analyses of frontocortical, hippocampal, and striatal AEA, 2‐AG, PEA, and OEA concentrations revealed that their respective baseline concentrations were not influenced by the mouse genotype. On the other hand, the accumulation of frontocortical and/or hippocampal 2‐AG levels in JZL195‐pre‐treated mice was dependent on the mouse genotype. Thus, JZL195‐induced 2‐AG accumulation rates were diminished in the frontal cortex of mice lacking CB 1 receptors in glutamatergic neurons while their respective values were increased in the frontal cortex and hippocampus of mice lacking these receptors in astrocytes. These genotypic differences occurred with parallel and proportionate changes in the fractional rate constants for degradation of 2‐AG, thus providing a mechanism whereby the baseline levels of 2‐AG remained constant between genotypes. Besides suggesting a cell‐type‐specific control of frontocortical and/or hippocampal 2‐AG synthesis and degradation rates by CB 1 receptors, this study highlights the interest of assessing endocannabinoid turnover rates when questioning the status of the endocannabinoid system.In mice lacking CB 1 receptors from glutamatergic neurons (Glu‐CB 1 −/− ) or from astrocytes (GFAP‐CB 1 −/− ), frontocortical and hippocampal 2‐AG levels are not altered. Turnover studies indicate, however, that decreased 2‐AG synthesis occurs with decreased degradation in Glu‐CB 1 −/− mice, whereas the opposite is observed in GFAP‐CB 1 −/− mice. 2‐AG, 2‐arachidonoylglycerol; CB 1 , cannabinoid type‐1; Glu, glutamate.