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      Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice

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          Abstract

          Introduction

          This study was designed to investigate the putative anxiolytic-like activity of ultra-low doses of Gelsemium sempervirens ( G. sempervirens), produced according to the homeopathic pharmacopeia.

          Methods

          Five different centesimal (C) dilutions of G. sempervirens (4C, 5C, 7C, 9C and 30C), the drug buspirone (5 mg/kg) and solvent vehicle were delivered intraperitoneally to groups of ICR-CD1 mice over a period of 9 days. The behavioral effects were assessed in the open-field (OF) and light–dark (LD) tests in blind and randomized fashion.

          Results

          Most G. sempervirens dilutions did not affect the total distance traveled in the OF (only the 5C had an almost significant stimulatory effect on this parameter), indicating that the medicine caused no sedation effects or unspecific changes in locomotor activity. In the same test, buspirone induced a slight but statistically significant decrease in locomotion. G. sempervirens showed little stimulatory activity on the time spent and distance traveled in the central zone of the OF, but this effect was not statistically significant. In the LD test, G. sempervirens increased the % time spent in the light compartment, an indicator of anxiolytic-like activity, with a statistically significant effect using the 5C, 9C and 30C dilutions. These effects were comparable to those of buspirone. The number of transitions between the compartments of the LD test markedly increased with G. sempervirens 5C, 9C and 30C dilutions.

          Conclusion

          The overall pattern of results provides evidence that G. sempervirens acts on the emotional reactivity of mice, and that its anxiolytic-like effects are apparent, with a non-linear relationship, even at high dilutions.

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          Most cited references68

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          Measuring normal and pathological anxiety-like behaviour in mice: a review.

          Measuring anxiety-like behaviour in mice has been mostly undertaken using a few classical animal models of anxiety such as the elevated plus-maze, the light/dark choice or the open-field tests. All these procedures are based upon the exposure of subjects to unfamiliar aversive places. Anxiety can also be elicited by a range of threats such as predator exposure. Furthermore, the concepts of "state" and "trait" anxiety have been proposed to differentiate anxiety that the subject experiences at a particular moment of time and that is increased by the presence of an anxiogenic stimulus, and anxiety that does not vary from moment to moment and is considered to be an "enduring feature of an individual". Thus, when assessing the behaviour of mice, it is necessary to increase the range of behavioural paradigms used, including animal models of "state" and "trait" anxiety. In the last few years, many mice with targeted mutations have been generated. Among them some have been proposed as animal models of pathological anxiety, since they display high level of anxiety-related behaviours in classical tests. However, it is important to emphasise that such mice are animal models of a single gene dysfunction, rather than models of anxiety, per se. Inbred strains of mice, such as the BALB/c line, which exhibits spontaneously elevated anxiety appear to be a more suitable model of pathological anxiety.
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            Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders.

            The peripheral-type benzodiazepine receptor is a mitochondrial protein expressed at high levels in steroid synthesizing tissues, including the glial cells of the brain. Peripheral-type benzodiazepine receptor binds cholesterol with high affinity and is a key element of the cholesterol mitochondrial import machinery responsible for supplying the substrate cholesterol to the first steroidogenic enzyme, thus initiating and maintaining neurosteroid biosynthesis. Neurosteroid formation and metabolism of steroid intermediates are critical components of normal brain function. Peripheral-type benzodiazepine receptor also binds with high affinity various classes of compounds. Upon ligand activation peripheral-type benzodiazepine receptor-dependent cholesterol transport into mitochondria is accelerated leading in increased formation of neuroactive steroids. These steroids, such as allopregnanolone, have been shown to be involved in various neurological disorders, such as anxiety and mood disorders. Thus, peripheral-type benzodiazepine receptor drug ligand-induced neuroactive steroid formation offers a means to regulate brain dysfunction. Peripheral-type benzodiazepine receptor basal expression is upregulated in a number of neuropathologies, including gliomas and neurodegenerative disorders, as well as in various forms of brain injury and inflammation. In Alzheimer's disease pathology neurosteroid biosynthesis is altered and a decrease in the intermediate 22R-hydroxycholesterol levels is observed. This steroid was found to exert neuroprotective properties against beta-amyloid neurotoxicity. Based on this observation, a stable spirostenol derivative showing to display neuroprotective properties was identified, suggesting that compounds developed based on critical intermediates of neurosteroid biosynthesis could offer novel means for neuroprotection. In conclusion, changes in peripheral-type benzodiazepine receptor and neurosteroid levels are part of the phenotype seen in neuropathology and neurological disorders and offer potential targets for new therapies.
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              The in vitro evidence for an effect of high homeopathic potencies--a systematic review of the literature.

              Systematic assessment of the in vitro research on high potency effects. Publications of experiments were collected through databases, experts, previous reviews, citation tracking. stepwise agitated dilutions <10(-23); cells or molecules from human or animal. Experiments were assessed with the modified SAPEH score. From 75 publications, 67 experiments (1/3 of them replications) were evaluated. Nearly 3/4 of them found a high potency effect, and 2/3 of those 18 that scored 6 points or more and controlled contamination. Nearly 3/4 of all replications were positive. Design and experimental models of the reviewed experiments were inhomogenous, most were performed on basophiles. Even experiments with a high methodological standard could demonstrate an effect of high potencies. No positive result was stable enough to be reproduced by all investigators. A general adoption of succussed controls, randomization and blinding would strengthen the evidence of future experiments.
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                Author and article information

                Contributors
                +39-45-8027554 , +39-45-8027554 , paolo.bellavite@univr.it
                Journal
                Psychopharmacology (Berl)
                Psychopharmacology
                Springer-Verlag (Berlin/Heidelberg )
                0033-3158
                1432-2072
                20 April 2010
                20 April 2010
                July 2010
                : 210
                : 4
                : 533-545
                Affiliations
                [1 ]Dipartimento di Patologia, Università di Verona, Strada Le Grazie, 37134 Verona, Italy
                [2 ]Department of Medicine and Public Health, University of Verona, Verona, Italy
                Article
                1855
                10.1007/s00213-010-1855-2
                2877813
                20401745
                daabd436-bd19-4821-aec7-0853510f1298
                © The Author(s) 2010
                History
                : 10 February 2010
                : 26 March 2010
                Categories
                Original Investigation
                Custom metadata
                © Springer-Verlag 2010

                Pharmacology & Pharmaceutical medicine
                ultra-low doses,gelsemine,open-field test,complementary medicine,animal models of anxiety,nanopharmacology,light–dark test,gelsemium sempervirens

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