IMIM - Institut Hospital del Mar d'Investigacions Mèdiques



"Orexins as novel therapeutic targets for post-traumatic stress disorder: Insights from animal models" a càrrec de Fernando Berrendero

Sala Ramón y Cajal (Plaça interior PRBB) a les 12 hores

En el marc de les sessions del Programa de neurociències, el proper divendres dia 21 de novembre a les 12:00 hores tindrà lloc a la Sala Ramon y Cajal (Pati interior del PRBB) la sessió que porta per títol "Orexins as novel therapeutic targets for post-traumatic stress disorder: Insights from animal models" impartida pel Dr. Fernando Berrendero, investigador del Grup de recerca en Neurofarmacologia del Departament de Ciències Experimentals i de la Salut de la UPF.

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Resum en anglès

Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction while hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor- 1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala infusion of SB334867 enhanced fear extinction. However, the injection of this antagonist in the infralimbic prefrontal cortex and the dorsal hippocampus did not modify fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear such as posttraumatic stress disorder and phobias.

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