Serotonin 2C receptor antagonist improves fear discrimination and subsequent safety signal recall
Autor: | Allison R. Foilb, John P. Christianson |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Indoles Aminopyridines Audiology Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Discrimination Psychological 0302 clinical medicine Conditioning Psychological Receptor Serotonin 5-HT2C medicine Serotonin 5-HT2 Receptor Antagonists Animals Discrimination learning Effects of sleep deprivation on cognitive performance Freezing Reaction Cataleptic Psychiatry Biological Psychiatry Pharmacology Electroshock Conditioning (Psychology) Recall test Classical conditioning Fear Inhibition Psychological 030104 developmental biology chemistry Mental Recall Anxiety medicine.symptom Psychology SB-242084 030217 neurology & neurosurgery |
Zdroj: | Progress in Neuro-Psychopharmacology and Biological Psychiatry. 65:78-84 |
ISSN: | 0278-5846 |
Popis: | 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-HT 2C receptor. 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-HT 2C receptor antagonist SB 242084 (0.25 or 1.0 mg/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 3 days of conditioning versus 5 days in the vehicle treated controls. These results suggest a novel therapeutic use for 5-HT 2C receptor antagonists to improve learning under stressful circumstances. Potential anatomical loci for 5-HT 2C receptor 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. |
Databáze: | OpenAIRE |
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