کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2572676 1129318 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Amygdala FAAH and anandamide: mediating protection and recovery from stress
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Amygdala FAAH and anandamide: mediating protection and recovery from stress
چکیده انگلیسی


• Fatty acid amide hydrolase (FAAH) regulates CB1R signaling in anxiety mediating brain regions.
• Increasing endogenous levels of anandamide could modulate anxiety and stress.
• Inhibition of FAAH can rescue impairments in fear extinction and ameliorate chronic stress.
• FAAH inhibitors have promise as a novel approach to treating anxiety disorders.

A long-standing literature linking endocannabinoids (ECBs) to stress, fear, and anxiety has led to growing interest in developing novel anxiolytics targeting the ECB system. Following rapid on-demand biosynthesis and degradation upon neuronal activation, the ECB N-arachidonoylethanolamide (anandamide, AEA) is actively degraded by the serine hydrolase enzyme, fatty acid amide hydrolase (FAAH). Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA and increase neuronal excitability in a key anxiety-mediating region – the basolateral amygdala (BLA). Gene deletion or pharmacological inhibition of FAAH prevents stress-induced reductions in AEA and associated increases in BLA dendritic hypertrophy and anxiety-like behavior. Additionally, inhibition of FAAH facilitates long-term fear extinction and rescues deficient fear extinction in rodent models by enhancing AEA–CB1 (cannabinoid type 1) receptor signaling and synaptic plasticity in the BLA. These preclinical findings propose restoring deficient BLA AEA levels by pharmacologically inhibiting FAAH as a mechanism to therapeutically mitigate the effects of traumatic stress.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 34, Issue 11, November 2013, Pages 637–644
نویسندگان
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