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Serotonin 2C receptor antagonist improves fear discrimination and subsequent safety signal recall.

Abstract：

UNLABELLED: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-HT2Creceptor. Using a fear discrimination paradigm where a danger signal conditioned stimulus (CS+) co-terminates with a mild footshock and a safety signal (CS-) indicates the absence of shock, we demonstrate that danger/safety discrimination and fear inhibition develop over the course of 4 daily conditioning sessions. Systemic administration of the 5-HT2Creceptor antagonist SB 242084 (0.25 or 1.0mg/kg) prior to conditioning reduced behavioral freezing during conditioning, and 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 3days of conditioning versus 5days in the vehicle treated controls. These results suggest a novel therapeutic use for 5-HT2Creceptor antagonists to improve learning under stressful circumstances. Potential anatomical loci for 5-HT2Creceptor modulation of fear discrimination learning and cognitive performance enhancement are discussed. ETHICAL STATEMENT:John P. Christianson and Allison R. Foilb, the authors, verify that animal research was carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) and all procedures involving animals were reviewed and approved by the Boston College Animal Care and Use Committee. All efforts were made to limit the number of animals used and their suffering.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Foilb AR,Christianson JP

doi

10.1016/j.pnpbp.2015.08.017

subject

Has Abstract

pub_date

2016-02-04 00:00:00

pages

78-84

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(15)30036-1

journal_volume

pub_type

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Serotonin 2C receptor antagonist improves fear discrimination and subsequent safety signal recall.