Candesartan ameliorates impaired fear extinction induced by innate immune activation

Autor: María M. Quiñones, Bethzaly Velazquez, James T. Porter, Lizette Maldonado
Rok vydání: 2016
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
medicine.medical_specialty
Immunology
Tetrazoles
Context (language use)
Amygdala
Article
Extinction
Psychological
Developmental psychology
Rats
Sprague-Dawley
Stress Disorders
Post-Traumatic
Random Allocation
03 medical and health sciences
Behavioral Neuroscience
0302 clinical medicine
Immune system
Internal medicine
Conditioning
Psychological
medicine
Animals
Fear conditioning
Innate immune system
Endocrine and Autonomic Systems
Biphenyl Compounds
Fear
social sciences
Extinction (psychology)
musculoskeletal system
Angiotensin II
Immunity
Innate
humanities
Rats
Candesartan
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Mental Recall
Models
Animal
Benzimidazoles
Cues
Psychology
Stress
Psychological
geographic locations
030217 neurology & neurosurgery
medicine.drug
Zdroj: Brain, Behavior, and Immunity. 52:169-177
ISSN: 0889-1591
DOI: 10.1016/j.bbi.2015.10.017
Popis: Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 hrs after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD.
Databáze: OpenAIRE
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