Fatty acid amide hydrolase inhibitors produce rapid anti-anxiety responses through amygdala long-term depression in male rodents

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Fatty acid amide hydrolase inhibitors produce rapid anti-anxiety responses through amygdala long-term depression in male rodents


نویسنده	duan t. ,gu n. ,wang y. ,wang f. ,zhu j. ,fang y. ,shen y. ,han j. ,zhang x.
منبع	journal of psychiatry and neuroscience - 2017 - دوره : 42 - شماره : 4 - صفحه:230 -241
چکیده	Pathological anxiety is the most common type of psychiatric disorder. the current first-line anti-anxiety treatment,selective serotonin/noradrenaline reuptake inhibitors,produces a delayed onset of action with modest therapeutic and substantial adverse effects,and long-term use of the fast-acting anti-anxiety benzodiazepines causes severe adverse effects. inhibition of the fatty acid amide hydrolase (faah),the endocannabinoid n-arachidonoylethanolamine (aea) degradative enzyme,produces anti-anxiety effects without substantial “unwanted effects” of cannabinoids,but its anti-anxiety mechanism is unclear. methods: we used behavioural,electrophysiological,morphological and mutagenesis strategies to assess the anti-anxiety mechanism of the faah inhibitors pf3845 and urb597. results: pf3845 exerts rapid and long-lasting anti-anxiety effects in mice exposed acutely to stress or chronically to the stress hormone corticosterone. pf3845-induced anti-anxiety effects and in vivo long-term depression (ltd) of synaptic strength at the prefrontal cortical input onto the basolateral amygdala neurons are abolished in mutant mice without cb1 cannabinoid receptors (cb1r) in brain astroglial cells,but are conserved in mice without cb1r in glutamatergic neurons. blockade of glutamate n-methyl-d-aspartate receptors and of synaptic trafficking of glutamate ampa receptors also abolishes pf3845-induced anti-anxiety effects in mice and ltd production in rats. urb597 produces similar anti-anxiety effects,which are abolished by blockade of ltd induction in mice. limitations: the determination of faah in which types of brain cells contribute to aea degradation for the maintenance of amygdala interstitial aea has yet to be determined. conclusion: we propose that the rapid anti-anxiety effects of faah inhibition are due to aea activation of astroglial cb1r and subsequent basolateral amygdala ltd in vivo. © 2017 joule inc. or its licensors.

آدرس	university of ottawa institute of mental health research at the royal,ottawa,on, Canada, university of ottawa institute of mental health research at the royal,ottawa,on, Canada, university of ottawa institute of mental health research at the royal,ottawa,on,canada,department of psychiatry,xijing hospital,fourth military medical university,xian, China, university of ottawa institute of mental health research at the royal,ottawa,on, Canada, university of ottawa institute of mental health research at the royal,ottawa,on, Canada, university of ottawa institute of mental health research at the royal,ottawa,on,canada,the shanghai mental health center,shanghai jiao tong university school of medicine,shanghai, China, university of ottawa institute of mental health research at the royal,ottawa,on,canada,department of psychiatry,shanghai 10th people’s hospital,affiliated hospital of tongji university,shanghai, China, key laboratory of modern teaching technology,shaanxi normal university,xi’an,shaanxi, China, university of ottawa institute of mental health research at the royal,ottawa,on, Canada



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