The GABAA-Benzodiazepine Receptor Antagonist Flumazenil Abolishes the Anxiolytic Effects of the Active Constituents of Crocus sativus L. Crocins in Rats

Anxiety is a chronic severe psychiatric disorder. Crocins are among the various bioactive components of the plant Crocus sativus L. (Iridaceae) and their implication in anxiety is well-documented. However, which is the mechanism of action underlying the anti-anxiety effects of crocins remains unknown. In this context, it has been suggested that these beneficial effects might be ascribed to the agonistic properties of these bioactive ingredients of saffron on the GABA type A receptor. The current experimentation was undertaken to clarify this issue in the rat. For this research project, the light/dark and the open field tests were used. A single injection of crocins (50 mg/kg, i.p., 60 min before testing) induces an anti-anxiety-like effect revealed either in the light-dark or open field tests. Acute administration of the GABAA-benzodiazepine receptor antagonist flumazenil (10 mg/kg, i.p., 30 min before testing) abolished the above mentioned anxiolytic effects of crocins. The current findings suggest a functional interaction between crocins and the GABAA receptor allosteric modulator flumazenil on anxiety.

Anxiolytic-like effect of Bifidobacterium adolescentis IM38 in mice with or without immobilisation stress

To better understand the role of gut microbiota in the anxiety, we isolated bifidobacteria and lactobacilli from the human faecal microbiota, investigated their inhibitory effects on the expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-α in lipopolysaccharide-stimulated macrophages, and examined the anxiolytic-like effect of Bifidobacterium adolescentis IM38 in mice treated with or without immobilisation stress using the elevated plus maze (EPM) task. Oral administration of IM38 at a dose of 1×109 cfu/mouse showed a significant anxiolytic-like effect both in mice exposed to immobilisation stress and in control mice using the EPM test (P<0.05). Moreover, IM38 treatment significantly increased the amount of time spent on open arms and open arm entries. The anxiolytic-like effect of IM38 was comparable to that of buspirone (1 mg/kg). Moreover, this anxiolytic-like effect was blocked by treatment with flumazenil (3 mg/kg, i.p.), a benzodiazepine receptor antagonist, but was not affected by treatment with bicuculine or WAY-100635. IM38 treatment also reduced the blood levels of corticosterone and IL-6 in mice with or without immobilisation stress, whereas this effect was abolished by treatment with flumazenil. IM38 treatment also reduced the blood TNF-α level in mice subjected to immobilisation stress but not in normal control mice. Treatment with flumazenil also significantly increased TNF-α and IL-6 levels in immobilisation stress-free mice treated with IM38. These findings suggest that IM38 may attenuate anxiety through modulation of the benzodiazepine site on the GABAA receptor and modulate stress-related cytokine expression.

Phenotype of GABA-transaminase deficiency

Objective:We report a case series of 10 patients with γ-aminobutyric acid (GABA)–transaminase deficiency including a novel therapeutic trial and an expanded phenotype.Methods:Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil.Results:All patients presented with neonatal or early infantile-onset encephalopathy; other features were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth. EEGs showed burst-suppression, modified hypsarrhythmia, multifocal spikes, and generalized spike-wave. Five of the 10 patients are currently alive with age at last follow-up between 18 months and 9.5 years. Treatment with continuous flumazenil was implemented in 2 patients. One patient, with a milder phenotype, began treatment at age 21 months and has continued for 20 months with improved alertness and less excessive adventitious movements. The second patient had a more severe phenotype and was 7 years of age at initiation of flumazenil, which was not continued.Conclusions:GABA-transaminase deficiency presents with neonatal or infantile-onset encephalopathy including hypersomnolence and choreoathetosis. A widened phenotypic spectrum is reported as opposed to lethality by 2 years of age. The GABA-A benzodiazepine receptor antagonist flumazenil may represent a therapeutic strategy.

Evidence for the involvement of the GABA-ergic pathway in the anticonvulsant activity of the roots bark aqueous extract of Anthocleista djalonensis A. Chev. (Loganiaceae)

Background:The root bark ofMethods:To investigate the anticonvulsant effects and the possible mechanisms of this plant, an aqueous extract ofResults:This extract significantly protected mice against bicuculline-induced motor seizures. It provided 80% protection against picrotoxin-induced tonic-clonic seizures, and strongly antagonized convulsions induced by pilocarpine. AEAD also protected 100% of mice against pentylenetetrazole-induced seizures. Flumazenil, a central benzodiazepine receptor antagonist and FG7142, a partial inverse agonist in the benzodiazepine site of the GABAConclusions:The effects of