Rapid anti-PTSD-like activity of the TSPO agonist YL-IPA08: Emphasis on brain GABA, neurosteroids and HPA axis function.
Behav Brain Res
; 379: 112320, 2020 02 03.
Article
en En
| MEDLINE
| ID: mdl-31669345
ABSTRACT
There is a serious need for fast-acting drugs to treat post-traumatic stress disorder (PTSD). Our previous studies revealed that YL-IPA08, a novel small-molecule TSPO agonist, exerted significant anti-PTSD effects in various animal models. However, the onset time of YL-IPA08 and its underlying mechanisms remain unclear. In the present study, we first investigated the time course of YL-IPA08 compared to selective serotonin reuptake inhibitors (SSRIs) in the well-known time-dependent sensitization model of PTSD. YL-IPA08 required only 2-4 days of treatment to take effect in behavioural models of PTSD, whereas sertraline required 7-8 days. Furthermore, the mechanism study revealed that YL-IPA08 elicited anti-PTSD-like effects associated with increased GABA levels and allopregnanolone efflux in the hippocampus and prefrontal cortex and increased corticosterone levels in the serum after only 5 days of treatment, whereas sertraline required 9 days. Our results demonstrate that YL-IPA08 can exert fast-onset anti-PTSD-like effects, and its mechanisms may be related to the increased GABA levels, allopregnanolone efflux and the hypothalamic-pituitary-adrenal (HPA) axis function.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pregnanolona
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Piridinas
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Trastornos por Estrés Postraumático
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Conducta Animal
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Corticosterona
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Proteínas Portadoras
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Inhibidores Selectivos de la Recaptación de Serotonina
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Corteza Prefrontal
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Ácido gamma-Aminobutírico
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Hipocampo
Límite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Año:
2020
Tipo del documento:
Article
País de afiliación:
China