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Candesartan ameliorates impaired fear extinction induced by innate immune activation.
Quiñones, María M; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T.
Afiliação
  • Quiñones MM; Dept. of Clinical Psychology, Ponce Health Sciences University, Ponce, PR, United States.
  • Maldonado L; Dept. of Chemistry, Pontifical Catholic University of Puerto Rico, Ponce, PR, United States.
  • Velazquez B; Dept. of Basic Sciences, Ponce Health Sciences University-School of Medicine/Ponce Research Institute, Ponce, PR, United States.
  • Porter JT; Dept. of Basic Sciences, Ponce Health Sciences University-School of Medicine/Ponce Research Institute, Ponce, PR, United States. Electronic address: jporter@psm.edu.
Brain Behav Immun ; 52: 169-177, 2016 Feb.
Article em En | MEDLINE | ID: mdl-26520214
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 h 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtornos de Estresse Pós-Traumáticos / Tetrazóis / Benzimidazóis / Extinção Psicológica / Medo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtornos de Estresse Pós-Traumáticos / Tetrazóis / Benzimidazóis / Extinção Psicológica / Medo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article