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Interaction of 2‐arachidonyl glycerol with the glutamatergic system in anxiety
Author(s) -
ElAlfy Abir T,
Gole Monica,
AlRahim Md
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.799.3
The objective of this present study was to determine the interactive effects of the endocannabinoid 2‐arachidonyl glycerol (2‐AG) and the selective mGluR5 antagonist MTEP on anxiety using the mouse elevated plus maze test. The dose responses for 2‐AG, MTEP, and combinations of these two compounds were established using male Swiss Webster mice. There was an overall significant anxiolytic‐like effect (p<0.05) obtained with 2‐AG. A significant anxiolytic effect was obtained with the 3 mg/kg dose of MTEP (p<0.05). However, MTEP blocked the anxiolytic‐like effect produced by 2‐AG while 2‐AG blocked the anxiolytic effect of MTEP 3 mg/kg. Glutamate levels were significantly elevated by the 2‐AG 0.05 mg/kg dose (p<0.01) in different brain regions. On the other hand, MTEP administration induced a significant decrease of glutamate levels. The combined administration of the two compounds also affected the glutamate levels in an antagonistic manner. The GABA levels were significantly elevated (p<0.01) by the low doses of 2‐AG in the prefrontal cortex and hippocampus. MTEP significantly reduced the GABA levels only at the 6 mg/kg dose (p<0.05) in the prefrontal cortex. The combined administration of 2‐AG and MTEP significantly reduced the GABA levels (p<0.001) in both studied brain regions. Further studies are needed to delineate the extent and mechanism of interaction between 2‐AG and MTEP in anxiety. Grant number 5P20RR021929 from National Center of Research Resources