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Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase
TLDR
Results indicate that FAAH is a key regulator of anandamide signaling in vivo, setting an endogenous cannabinoid tone that modulates pain perception, and may represent an attractive pharmaceutical target for the treatment of pain and neuropsychiatric disorders.
Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects
TLDR
2-AG endogenously modulates several behavioral processes classically associated with the pharmacology of cannabinoids and point to overlapping and unique functions for 2-AG and anandamide in vivo, indicating a functional segregation of endocannabinoid signaling pathways in vivo.
Endocannabinoid Hydrolysis Generates Brain Prostaglandins That Promote Neuroinflammation
TLDR
These findings identify MAGL as a distinct metabolic node that couples endocannabinoid to prostaglandin signaling networks in the nervous system and suggest that inhibition of this enzyme may be a new and potentially safer way to suppress the proinflammatory cascades that underlie neurodegenerative disorders.
Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system
TLDR
Individual endocannabinoids generate distinct analgesic profiles that are either sustained or transitory and associated with agonism and functional antagonism of the brain cannabinoid system, respectively.
Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo
TLDR
A selective and efficacious dual FAAH/MAGL inhibitor is described and it is shown that this agent exhibits broad activity in the tetrad test for CB1 agonism, causing analgesia, hypomotilty, and catalepsy, indicating that AEA and 2-AG signaling pathways interact to regulate specific behavioral processes in vivo, including those relevant to drug abuse.
Reversible Inhibitors of Fatty Acid Amide Hydrolase That Promote Analgesia: Evidence for an Unprecedented Combination of Potency and Selectivity
TLDR
A class of α-keto-heterocycles are identified that show unprecedented selectivity for FAAH relative to other mammalian hydrolases, and, when administered to rodents, raise central nervous system levels of anandamide and promote cannabinoid receptor 1-dependent analgesia in several assays of pain sensation.
Systemic or intrahippocampal cannabinoid administration impairs spatial memory in rats
TLDR
Dissociation between choice accuracy in the radial-maze and other cannabinoid pharmacological effects suggests that the working memory deficits produced by cannabinoids may be mediated by cannabinoid receptors in the hippocampus.
Evaluation of CB1 receptor knockout mice in the Morris water maze.
TLDR
Results provide strong evidence that cannabinoids disrupt working memory through a CB(1) receptor mechanism of action, and suggest that the endocannabinoid system may have a role in facilitating extinction and/or forgetting processes.
Blockade of Endocannabinoid-Degrading Enzymes Attenuates Neuropathic Pain
TLDR
The data indicate that inhibition of FAAH and MAGL reduces neuropathic pain through distinct receptor mechanisms of action and present viable targets for the development of analgesic therapeutics.
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