Background
Cannabinoid agonists are potential therapeutic agents because of their antinociceptive
and anxiolytic-like effects, although an important caveat to their use is the possible
adverse responses related to memory impairment. An alternative approach to circumvent
this limitation consists of enhancing the concentration of the endocannabinoids anandamide
and 2-arachidonoylglycerol.
Methods
Using low doses of the specific inhibitors of the endocannabinoid metabolizing enzymes
fatty acid amide hydrolase, URB597, and monoacylglycerol lipase, JZL184, we analyzed
their acute and chronic effects on memory consolidation, anxiolytic-like effects,
and nociception in mice (n = 6–12 per experimental group).
Results
We show that anandamide is a central component in the modulation of memory consolidation,
whereas 2-arachidonoylglycerol is not involved in this process. Interestingly, both
URB597 and JZL184 induce anxiolytic-like effects through different cannabinoid receptors.
In addition, the results show that the antinociceptive and anxiolytic-like responses
of both inhibitors, as well as their acute effects on memory consolidation, are maintained
after chronic treatment.
Conclusions
These results dissociate the role of anandamide and 2-arachidonoylglycerol in memory
consolidation and anxiety and reveal the interest of cannabinoid receptor 2 as a novel
target for the treatment of anxiety-related disorders.
Key Words
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Article info
Publication history
Published online: June 20, 2011
Accepted:
April 27,
2011
Received in revised form:
April 26,
2011
Received:
November 24,
2010
Footnotes
Authors AB-G and EP contributed equally to this work.
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
