Serotonin 2C receptor antagonist improves fear discrimination and subsequent safety signal recall.
Serotonin 2C receptor antagonist improves fear discrimination and subsequent safety signal recall.
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DOI：
10.1016/j.pnpbp.2015.08.017
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发表时间：
2016-02-04
影响因子：
5.6
通讯作者：
Christianson JP
中科院分区：
文献类型：
--
作者：
Foilb AR;Christianson JP
The capacity to discriminate between safety and danger is fundamental for survival, but is disrupted in individuals with posttraumatic stress disorder (PTSD). Acute stressors cause a release of serotonin (5-HT) in the forebrain, which is one mechanism for enhanced fear and anxiety; these effects are mediated by the 5-HT2C receptor. Using a fear discrimination paradigm where a danger signal conditioned stimulus (CS+) coterminates with a mild footshock and a safety signal (CS-) indicates the absence of shock, we demonstrate that danger/safety discrimination and fear inhibition develops over the course of 4 daily conditioning sessions. Systemic administration of the 5-HT2C receptor antagonist SB 242084 (0.25 or 1.0 mg/kg) prior to conditioning reduced behavioral freezing during conditioning, improved learning and subsequent inhibition of fear by the safety signal. Discrimination was apparent in the first recall test, and discrimination during training was evident after 3 days of conditioning versus 5 days in the vehicle treated controls. These results suggest a novel therapeutic use for 5-HT2C receptor antagonists to improve learning under stressful circumstances. Potential anatomical loci for 5-HT2C receptor modulation of fear discrimination learning and cognitive performance enhancement are discussed.
