Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis.
PLoS One
; 9(7): e101450, 2014.
Article
em En
| MEDLINE
| ID: mdl-24988461
ABSTRACT
Post-traumatic stress disorder (PTSD) is a debilitating anxiety disorder that may develop after an individual has experienced or witnessed a severe traumatic event. It has been shown that the 18 kDa translocator protein (TSPO) may be correlated with PTSD and that the TSPO ligand improved the behavioral deficits in a mouse model of PTSD. Midazolam, a ligand for TSPO and central benzodiazepine receptor (CBR), induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether midazolam ameliorates PTSD behavior in rats as assessed by the single prolonged stress (SPS) model. The SPS rats received daily Sertraline (Ser) (15 mg/kg, i.p.) [corrected] and midazolam (0.125, 0.25, 0.5, and 1 mg/kg, i.p.) [corrected] during the exposure to SPS and behavioral assessments, which included the open field (OF) test, the contextual fear paradigm (CFP), and the elevated plus-maze (EPM). The results showed that, like Ser (15 mg/kg, i.p.) [corrected], midazolam (0.25 and 0.5 mg/kg, i.p.) [corrected] significantly reversed the behavioral deficiencies of the SPS rats, including PTSD-associated freezing and anxiety-like behavior but not the effects on spontaneous locomotor activity. In addition, the anti-PTSD effects of midazolam (0.5 mg/kg, i.p.) [corrected] were antagonized by the TSPO antagonist PK11195 (3 mg/kg, i.p.), the CBR antagonist flumazenil (15 mg/kg, i.p.) [corrected] and the inhibitor of steroidogenic enzymes finasteride (30 mg/kg, i.p.) [corrected], which by themselves had no effect on PTSD-associated freezing and anxiety-like behavior. In summary, this study demonstrated that midazolam improves the behavioral deficits in the SPS model through dual TSPO and CBR and neurosteroidogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos de Estresse Pós-Traumáticos
/
Ansiolíticos
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Midazolam
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Proteínas de Transporte
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Receptores de GABA-A
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Neurotransmissores
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2014
Tipo de documento:
Article