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

Progress in Neuro-psychopharmacology & Biological Psychiatry
Allison R Foilb, John P Christianson

Abstract

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 discr...Continue Reading

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Citations

Jul 18, 2016·Neurobiology of Learning and Memory·Harriet L L DayCarl W Stevenson
Aug 16, 2016·Neurobiology of Learning and Memory·Allison R FoilbJohn P Christianson
Oct 8, 2016·Organic & Biomolecular Chemistry·Raphaël Lafleur-Lambert, John Boukouvalas
Mar 28, 2017·Reviews in the Neurosciences·Alfredo Meneses
Dec 17, 2017·Learning & Memory·Allison R FoilbJohn P Christianson
Sep 22, 2020·Behavioural Brain Research·I NahmoudE Likhtik
May 24, 2021·Neuroscience and Biobehavioral Reviews·Patrick A F Laing, Ben J Harrison

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