Repeated administration of AC-5216, a ligand for the 18kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder

Qiu, Zhi-Kun; Zhang, Liming; Zhao, Nan; Chen, Hongxia; You-zhi, Zhang; Li, Yanqin; Mi, Tianyue; Zhou, Wenwen; Li, Yang; Yang, Ri-Fang; Xu, Jiang; Li, Yunfeng

doi:10.1016/j.pnpbp.2013.04.010

Cited by 53 publications

(46 citation statements)

References 57 publications

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“…The experimental procedure was carried out as described previously (Qiu et al 2013;Zhang et al 2012). For the training session, a plexiglass chamber (20×10×10 cm) with a stainless-steel grid floor (9-mm interval) was used.…”

Section: Drugs and Treatmentsmentioning

confidence: 99%

Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder

Zhang¹,

Zhou

et al. 2014

Psychopharmacology

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This study investigated the effectiveness of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in alleviating the enhanced anxiety and fear response in both a mouse model of PTSD induced by inescapable electric foot shocks and a rat model of PTSD induced by a time-dependent sensitization (TDS) procedure. First, we evaluated the effect of ketamine on behavioral deficits in a mouse model of PTSD that consisted of foot shocks followed by three situational reminders. Our results showed that the aversive procedure induced several behavioral deficiencies, such as increased freezing behavior and anxiety, as well as reduced time spent in an aversive-like context, which were reversed by repeated treatment with ketamine. The effect of ketamine on behavioral changes after exposure to TDS was also investigated, and the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured. The results revealed that after TDS, the rats showed a significant increase in contextual freezing and a decrease in the percentage of time spent in and numbers of entries into open arms in the elevated plus maze test. As a positive control drug, sertraline (Ser, 15 mg/kg, i.g.), a selective serotonin reuptake inhibitor (SSRI) ameliorated these behavioral deficits. These behavioral effects were mimicked by chronic ketamine treatment. Furthermore, ketamine normalized the decreased BDNF level in the hippocampus in post-TDS rats. Taken together, these results suggest that ketamine exerts a therapeutic effect on PTSD that might be at least partially mediated by an influence on BDNF signaling in the hippocampus.

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Section: Drugs and Treatmentsmentioning

confidence: 99%

Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder

Zhang¹,

Zhou

et al. 2014

Psychopharmacology

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“…The experimental procedure was conducted as described previously (Zhang et al, 2012;Qiu et al, 2013). For the training session, a Plexiglas chamber (20 × 10 × 10 cm) with a stainless steel grid floor (9 mm interval) was used.…”

Section: Behavioural Experimentsmentioning

confidence: 99%

Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in animal models of post-traumatic stress disorder

Zhang¹,

Qiu²,

Zhao³

et al. 2014

Int. J. Neuropsychopharm.

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Recently, the translocator protein (18 kDa) (TSPO), previously called peripheral benzodiazepine receptor (PBR) and both the starting point and an important rate-limiting step in neurosteroidogenesis, has received increased attention in the pathophysiology of post-traumatic stress disorder (PTSD) because it affects the production of neurosteroids, reinforcing the hypothesis that selective TSPO ligands could potentially be used as anti-PTSD drugs. As expected, we showed that chronic treatment with YL-IPA08 [N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl)-7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, caused significant suppression of enhanced anxiety and contextual fear induced in the inescapable electric foot-shock-induced mouse model of PTSD and the time-dependent sensitization (TDS) procedure. These effects were completely blocked by the TSPO antagonist PK11195. Furthermore, YL-IPA08 could increase the level of allopregnanolone in the prefrontal cortex and serum of post-TDS rats, and these effects were antagonized by PK11195. In summary, the findings from the current study showed that YL-IPA08, a potent and selective TSPO ligand, had a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.

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“…Also, XBD173 exerted anti-panic effects in rodents and humans, in the absence of sedation, tolerance development and withdrawal symptoms [65]. More recently, this compound has been shown to improve the behavioral deficits involving freezing and anxiety-like behaviors in a mouse model of post-traumatic stress disorder [66]. However, Owen et al [67] reported high TSPO binding variability of XBD173 across human subjects, and XBD173 did not show superiority over placebo in a phase II trial with patients with generalized anxiety disorder [68].…”

Section: Tspo Ligands and Psychiatric Disordersmentioning

confidence: 99%

“…Mouse model of posttraumatic stress disorder XBD173 Decreased freezing and anxiolytic-like behaviors [66].…”

Section: Experimental Models Tspo Ligands Effectmentioning

confidence: 99%

Therapeutic actions of translocator protein (18 kDa) ligands in experimental models of psychiatric disorders and neurodegenerative diseases

Arbo

Benetti

Garcia-Segura

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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Repeated administration of AC-5216, a ligand for the 18kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder

Cited by 53 publications

References 57 publications

Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder

Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder

Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in animal models of post-traumatic stress disorder

Therapeutic actions of translocator protein (18 kDa) ligands in experimental models of psychiatric disorders and neurodegenerative diseases

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