Abstract：
BACKGROUND:The current effective treatment options for posttraumatic stress disorder (PTSD) are limited, and therefore the need to explore new treatment strategies is critical. Pharmacological inhibition of the renin-angiotensin system is a common approach to treat hypertension, and emerging evidence highlights the importance of this pathway in stress and anxiety. A recent clinical study from our laboratory provides evidence supporting a role for the renin-angiotensin system in the regulation of the stress response in patients diagnosed with PTSD. METHODS:With an animal model of PTSD and the selective angiotensin receptor type 1 (AT1) antagonist losartan, we investigated the acute and long-term effects of AT1 receptor inhibition on fear memory and baseline anxiety. After losartan treatment, we performed classical Pavlovian fear conditioning pairing auditory cues with footshocks and examined extinction behavior, gene expression changes in the brain, as well as neuroendocrine and cardiovascular responses. RESULTS:After cued fear conditioning, both acute and 2-week administration of losartan enhanced the consolidation of extinction memory but had no effect on fear acquisition, baseline anxiety, blood pressure, and neuroendocrine stress measures. Gene expression changes in the brain were also altered in mice treated with losartan for 2 weeks, in particular reduced amygdala AT1 receptor and bed nucleus of the stria terminalis c-Fos messenger RNA levels. CONCLUSIONS:These data suggest that AT1 receptor antagonism enhances the extinction of fear memory and therefore might be a beneficial therapy for PTSD patients who have impairments in extinction of aversive memories.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Marvar PJ,Goodman J,Fuchs S,Choi DC,Banerjee S,Ressler KJdoi
10.1016/j.biopsych.2013.08.024subject
Has Abstractpub_date
2014-06-01 00:00:00pages
864-72issue
11eissn
0006-3223issn
1873-2402pii
S0006-3223(13)00777-4journal_volume
75pub_type
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pub_type： 临床试验,杂志文章
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pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期：1997-08-15 00:00:00
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journal_title：Biological psychiatry
pub_type： 杂志文章
doi：
更新日期：1982-06-01 00:00:00
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pub_type： 杂志文章
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更新日期：1997-11-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2016-04-01 00:00:00
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journal_title：Biological psychiatry
pub_type： 杂志文章,meta分析
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更新日期：2009-11-15 00:00:00
