Effects of stress and etifoxine on pentobarbital-induced loss of righting reflex in Balb/cByJ and C57BL/6J mice

Verleye, Marc; Heulard, Isabelle; Nuss, Philippe; Gillardin, Jean-Marie

doi:10.1016/j.neulet.2003.09.010

Cited by 11 publications

(12 citation statements)

References 18 publications

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“…The pentobarbital anesthesia duration was measured as the time from which righting reflex was lost until it was regained. The righting reflex was deemed to be lost when an animal did not right itself within 15 s of being placed on its back (Verleye, Heulard, Nuss, & Gillardin, 2003). Righting reflex was assessed every 60 s after TBI until a normal response was observed.…”

Section: Righting Reflex and Pentobarbital Anesthesia Duration Assementioning

confidence: 99%

Modified device for fluid percussion injury in rodents

Ouyang

Fan

et al. 2018

J of Neuroscience Research

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Fluid percussion (FP) injury model is a popular animal model of traumatic brain injury (TBI), but still there are some issues need to be addressed. To increase the validity and reliability of this technique, we adapted the FP device using electromagnetic protractor, stainless-steel cylinder, changing pressure transducer position, and foam pads to adjust the parameters of FP pulse. Besides, the adjusted FP device is more automatic. The FP pulse is promptly measured and displayed in a graphic user interface software. The modified device resulted in reliable FP pulse. The accuracy of the pendulum leveling was improved with using the electromagnetic protractor with slots. We then collected behavioral, cognition, electrophysiological, and immunohistochemical data to verify the percussion effects in TBI mice. Lateral fluid percussion injury (FPI) or sham treatment was administered at the right frontal motorsensory region of male C57BL/6J mice. TBI mice showed evident motor, cognitive, and functional impairments, characterized by evaluation of neurological, righting, geotaxis and cliff aversion reflexes, limb asymmetrical use, rotarod running, and Morris water maze testing. The neurobehavioral damages were scaled with histopathological findings. Further, the overall firing rates and theta powers in hippocampal CA1 were significantly reduced in TBI mice compared to sham mice at Days 2 and 3 after electrode implanting. The adapted device induced effects on behavior and biology in mice that agree with existing models. These findings confirmed the validity of adjustments, and the modified device may boost the interest in TBI studies.

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Section: Righting Reflex and Pentobarbital Anesthesia Duration Assementioning

confidence: 99%

Modified device for fluid percussion injury in rodents

Ouyang

Fan

et al. 2018

J of Neuroscience Research

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“…Действительно, в эксперимен-те этифоксин влияет на восстанавливающий рефлекс в пен-тобарбиталовой модели потери ориентации [16]. Лоразепам может существенно увеличивать время восстановления по-сле дезориентации (что, заметим, полностью соответствует понятию о лоразепаме как о сильнодействующем снотвор-ном с атаксическим эффектом [17]).…”

Section: этифоксинunclassified

Effects of etifoxine: Chemoreactome simulation

Торшин

Громова

Федотова

et al. 2016

RJTAO

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Этифоксин1 превосходит большинство бензодиазепи-нов по выраженности ГАМК-ергического транквилизирую-щего эффекта, обладает антиконвульсантными свойствами [1]. В отличие от бензодиазепинов этифоксин связывается с аллостерическим сайтом в молекуле ГАМК-рецептора, что приводит к усилению активности рецептора под воздейст-вием эндогенного ГАМК. Кроме того, этифоксин осущест-вляет модуляцию ГАМК-ергической активности за счет ак-тивации синтеза нейростероидов, которые, как известно, повышают чувствительность ГАМК-А-рецепторов к ГАМК [2]. Описанные выше факты общеизвестны. Более деталь-ного сравнения фармакодинамических и фармакокинети-

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“…However, homopentameric β2GABAARs are less sensitive to EFX than homopentameric β1GABAARs [24], suggesting that the nature of the α subunit might also play a role in EFX-GABAARs interaction. In addition, at anxiolytic doses, EFX has no sedative effects nor locomotion impairment in humans [19] or rodents [30] and this could hardly be explained by the equal potency of EFX on α2GABAAR and α1GABAAR since the latter is associated with sedation [10,12]. Thus, we hypothesized that the pharmacological profile of EFX reflects different sensitivities of all α subtypes containing-GABAARs.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we first compared EFX and BZP in anxiolysis, sedation and locomotor impairment behavioral tests in acute conditions, in mice. The pharmacological effects of both EFX and BZP already appear after a single administration [8,9,29,30]. Here, we determined the anxiolytic doses of EFX and their possible influences on motor performance and arousal.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the GABAA receptor α subunit in the mode of action of etifoxine

Mattei

Taly

Soualah

et al. 2019

Pharmacological Research

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Etifoxine (EFX) is a non-benzodiazepine psychoactive drug which exhibits anxiolytic effects through a dual mechanism, by directly binding to GABAA receptors (GABAARs) and to the mitochondrial 18-kDa translocator protein, resulting in the potentiation of the GABAergic function. The b subunit subtype plays a key role in the EFX-GABAAR interaction, however this does not explain the anxiolytic effects of this drug. Here, we combined behavioral and electrophysiological experiments to challenge the role of the GABAAR a subunit in the EFX mode of action. After single administrations of anxiolytic doses (25-50 mg/kg, intraperitoneal), EFX did not induce any neurological nor locomotor impairments, unlike the benzodiazepine bromazepam (0.5-1 mg/kg, intraperitoneal). We established the EFX pharmacological profile on heteropentameric GABAARs constructed with α1 to α6 subunit expressed in Xenopus oocyte. Unlike what is known for benzodiazepines, neither the γ nor δ subunits influenced EFX-mediated potentiation of GABA-evoked currents. EFX acted first as a partial agonist on α2b3γ2S, α3b3γ2S, α6b3γ2S and α6b3d GABAARs, but not on α1b3γ2S, α4b3γ2S, α4b3d nor α5b3γ2S GABAARs. Moreover, EFX exhibited much higher positive allosteric modulation towards α2b3γ2S, α3b3γ2S and α6b3γ2S than for α1b3γ2S, α4b3γ2S and α5b3γ2S GABAARs. At 20 µM, corresponding to brain concentration at anxiolytic doses, EFX increased GABA potency to the highest extent for α3b3γ2S GABAARs. We built a docking model of EFX on α3β3γ2S GABAARs, which is consistent with a binding site located between α and β subunits in the extracellular domain. In conclusion, EFX preferentially potentiates α2b3γ2S and α3b3γ2S GABAARs, which might support its advantageous anxiolytic/sedative balance.

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Effects of stress and etifoxine on pentobarbital-induced loss of righting reflex in Balb/cByJ and C57BL/6J mice

Cited by 11 publications

References 18 publications

Modified device for fluid percussion injury in rodents

Modified device for fluid percussion injury in rodents

Effects of etifoxine: Chemoreactome simulation

Involvement of the GABAA receptor α subunit in the mode of action of etifoxine

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