The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Sandra E. File - One of the best experts on this subject based on the ideXlab platform.
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Animal Tests of Anxiety
Current Protocols in Neuroscience, 2004Co-Authors: Sandra E. File, Bernard Beer, Arnold S. Lippa, Morgen T. LippaAbstract:Animal Tests of anxiety are used to screen novel compounds for anxiolytic or anxiogenic activity, to investigate the neurobiology of anxiety, and to assess the impact of other occurrences such as exposure to predator odors or early rearing experiences. This unit presents protocols for the most commonly used Animal Tests of anxiety. The Geller-Seifter conflict test, the social interaction test, light/dark exploration, the elevated plus-maze, defensive burying, and the thirsty rat conflict. The protocols are described in terms of drug screening Tests, but can be modified easily for other purposes.
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Current Protocols in Neuroscience - Animal Tests of anxiety
Current Protocols in Pharmacology, 2004Co-Authors: Sandra E. File, Bernard Beer, Arnold S. Lippa, Morgen T. LippaAbstract:Animal Tests of anxiety are used to screen novel compounds for anxiolytic or anxiogenic activity, to investigate the neurobiology of anxiety, and to assess the impact of other occurrences such as exposure to predator odors or early rearing experiences. This unit presents protocols for the most commonly used Animal Tests of anxiety. The Geller-Seifter conflict test, the social interaction test, light/dark exploration, the elevated plus-maze, defensive burying, and the thirsty rat conflict. The protocols are described in terms of drug screening Tests, but can be modified easily for other purposes.
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involvement of 5 ht1a receptors in Animal Tests of anxiety and depression evidence from genetic models
Stress, 2003Co-Authors: David H Overstreet, Sandra E. File, Randall C Commissaris, Richard De La Garza, Darin J Knapp, Lewis S SeidenAbstract:Clinical studies have suggested the involvement of 5-HT1A receptors in anxiety and depressive disorders because partial 5-HT1A receptor agonists such as buspirone are therapeutic. The present review considers evidence from genetic Animal models that support a role for 5-HT1A receptors in anxiety-like and depressed-like behavior in Animals. Selective breeding for differential hypothermic responses to a selective 5-HT1A receptor agonist led to the development of the high DPAT sensitive (HDS) and low DPAT sensitive (LDS) lines of rats. The HDS rats differ from the LDS rats on several behavioral measures reflective of anxiety or depression, including reduced social interaction, reduced responding in a conflict task and exaggerated immobility in the forced swim test. However, they do not differ from the LDS rats in the elevated plus maze task, which is a commonly used test of anxiety. Nor do the HDS rats exhibit a typical anxiogenic response to the hippocampal administration of the 5-HT1A agonist. Although the HDS rats do exhibit elevations in 5-HT1A receptors in regions of the limbic cortex, it is not clear whether these increases account for the behavioral differences. Paradoxically, 5-HT1A receptor knockout mice also exhibit anxiety-like behavior in the plus maze, open field and conflict Tests compared to wild type mice. However, the knockouts exhibited less immobility in the forced swim test than wild type control mice. Recent studies using selective regional reinstatement of the receptor have implicated the postsynaptic 5-HT1A receptors in these changes in anxiety-like behavior. Thus, preliminary evidence from two different types of genetic Animal models suggests that anxiety-like behavior can arise if the 5-HT1A receptor function is eliminated or overexpressed. Further study with additional Tests of anxiety are needed to confirm this intriguing relationship.
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age associated sex differences in response to food deprivation in two Animal Tests of anxiety
Neuroscience & Biobehavioral Reviews, 2003Co-Authors: Rachel F Genn, Sonia Tucci, Amy Thomas, Jessica E Edwards, Sandra E. FileAbstract:The effects of mild food deprivation (7 days of food restricted to once daily feeding to maintain body weights at 85% of free-feeding weights) were examined in adult male and female and adolescent female rats tested in the elevated plus maze and social interaction Tests of anxiety. In adult male rats, food deprivation appeared to have an anxiolytic effect in the plus-maze as it significantly increased the percentage of entries onto open arms and the percentage of time spent on the open arms, without changing the number of closed arm entries. There were no effects of food deprivation in adult females, although in adolescent females food deprivation significantly increased the percentage of open arm entries rats. Adolescent female rats have female brains, but do not have circulating gonadal hormones and thus these results suggest that circulating female gonadal hormones are able to suppress some of the effects of mild food deprivation in the plus-maze. In the social interaction test, there were no effects of food deprivation in any group on the time spent in social interaction. There were opposite effects on locomotor activity in the adult male and female rats, with deprivation increasing activity in males and decreasing it in females. There were no effects of food deprivation on locomotor activity in the adolescent females, suggesting that circulating gonadal hormones were responsible for the bidirectional effects in the adult rats. In both Tests there were age-associated differences in the female rats, with the adolescent females being less anxious (higher percentage of open arm entries and increased social interaction) than the adults.
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social isolation modifies nicotine s effects in Animal Tests of anxiety
British Journal of Pharmacology, 2001Co-Authors: Survjit Cheeta, Elaine E Irvine, Sandra E. FileAbstract:These experiments determined whether the housing conditions of rats influenced the effects of nicotine in two Animal Tests of anxiety, social interaction and elevated plus-maze Tests. In Animals housed singly for 7 days, (−)nicotine (0.025 mg kg−1 s.c.) was ineffective, but 0.05, 0.1 and 0.25 mg kg−1 (s.c.) significantly increased the time spent in social interaction, without changing locomotor activity, thus indicating anxiolytic actions. (−)Nicotine (0.45 mg kg−1 s.c.) significantly reduced social interaction, indicating an anxiogenic effect. However, in group-housed Animals, (−)nicotine (0.025 mg kg−1 s.c.) had a significant anxiolytic effect in the social interaction test, but 0.01, 0.05, 0.1, 0.25 and 0.45 mg kg−1 were ineffective. (−)Nicotine (1 mg kg−1) reduced motor activity and social interaction in the group-housed Animals. In the elevated plus-maze, the time-course and the dose-response curve to nicotine were investigated. In both singly- and group-housed rats, (−) nicotine (0.1 – 0.45 mg kg−1 s.c.) decreased the per cent entries into, and per cent time spent on, the open arms, indicating anxiogenic effects. The housing condition influenced the time course, with significant effects at 5 and 30 min after injection in group-housed rats, and significant effects at 30 and 60 min in singly-housed rats. In the social interaction test there was no difference in the scores of the first and last rats removed from group cages, whereas the order of removal from the cages did affect the scores in the elevated plus-maze. These results provide further evidence that the two Animal Tests model distinct states of anxiety, and show how social isolation powerfully modifies both anxiolytic and anxiogenic effects of nicotine. British Journal of Pharmacology (2001) 132, 1389–1395; doi:10.1038/sj.bjp.0703991
Kristin Schirmer - One of the best experts on this subject based on the ideXlab platform.
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a european perspective on alternatives to Animal testing for environmental hazard identification and risk assessment
Regulatory Toxicology and Pharmacology, 2013Co-Authors: Stefan Scholz, Kristin Schirmer, Erika Sela, Ludek Blaha, Thomas Braunbeck, Malyka Galayburgos, Mauricio Garciafranco, Joaquin Guinea, Nils KluverAbstract:Tests with vertebrates are an integral part of environmental hazard identification and risk assessment of chemicals, plant protection products, pharmaceuticals, biocides, feed additives and effluents. These Tests raise ethical and economic concerns and are considered as inappropriate for assessing all of the substances and effluents that require regulatory testing. Hence, there is a strong demand for replacement, reduction and refinement strategies and methods. However, until now alternative approaches have only rarely been used in regulatory settings. This review provides an overview on current regulations of chemicals and the requirements for Animal Tests in environmental hazard and risk assessment. It aims to highlight the potential areas for alternative approaches in environmental hazard identification and risk assessment. Perspectives and limitations of alternative approaches to Animal Tests using vertebrates in environmental toxicology, i.e. mainly fish and amphibians, are discussed. Free access to existing (proprietary) Animal test data, availability of validated alternative methods and a practical implementation of conceptual approaches such as the Adverse Outcome Pathways and Integrated Testing Strategies were identified as major requirements towards the successful development and implementation of alternative approaches. Although this article focusses on European regulations, its considerations and conclusions are of global relevance.
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proposal to improve vertebrate cell cultures to establish them as substitutes for the regulatory testing of chemicals and effluents using fish
Toxicology, 2006Co-Authors: Kristin SchirmerAbstract:Cultures of vertebrate cells are widely applied in mechanistic studies in human toxicology as well as in toxicity identification in ecotoxicology. As in vitro models, they display many advantages over whole Animal experimentation, pertaining to such characteristics as availability, reproducibility and costs. As well, they satisfy the societal desire to reduce the number of Animals in toxicology. For these reasons vertebrate cell models also appear to be a desirable replacement for Animals in regulatory Tests. Several vertebrate cell models are now accepted for regulatory purposes in human health sciences, with the test for photocytotoxicity using the 3T3 mouse cell line being one example. However, an in vitro alternative to whole Animal Tests has not yet been established for regulatory risk assessment in ecotoxicology. This review sets out to outline why such a replacement has not yet been possible and explores avenues to improve vertebrate cell cultures so that a replacement of whole Animal Tests could more likely be achieved. Inasmuch as fish is the most widely used non-mammalian vertebrate in risk assessment and regulation, focus will be on the replacement, by in vitro vertebrate models, of fish.
Carl A K Borrebaeck - One of the best experts on this subject based on the ideXlab platform.
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a genomic biomarker signature can predict skin sensitizers using a cell based in vitro alternative to Animal Tests
BMC Genomics, 2011Co-Authors: Henrik Johansson, Malin Lindstedt, Annsofie Albrekt, Carl A K BorrebaeckAbstract:Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on Animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace Animal experiments with in vitro Tests displaying a higher predictive power. We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental Animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional Animal-based Tests.
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A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to Animal Tests
BMC Genomics, 2011Co-Authors: Henrik Johansson, Malin Lindstedt, Annsofie Albrekt, Carl A K BorrebaeckAbstract:Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on Animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace Animal experiments with in vitro Tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental Animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional Animal-based Tests.
Henrik Johansson - One of the best experts on this subject based on the ideXlab platform.
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a genomic biomarker signature can predict skin sensitizers using a cell based in vitro alternative to Animal Tests
BMC Genomics, 2011Co-Authors: Henrik Johansson, Malin Lindstedt, Annsofie Albrekt, Carl A K BorrebaeckAbstract:Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on Animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace Animal experiments with in vitro Tests displaying a higher predictive power. We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental Animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional Animal-based Tests.
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A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to Animal Tests
BMC Genomics, 2011Co-Authors: Henrik Johansson, Malin Lindstedt, Annsofie Albrekt, Carl A K BorrebaeckAbstract:Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on Animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace Animal experiments with in vitro Tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental Animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional Animal-based Tests.
Thomas Hartung - One of the best experts on this subject based on the ideXlab platform.
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Animal testing and its alternatives - the most important omics is economics
ALTEX, 2018Co-Authors: Lucy Meigs, Lena Smirnova, Marcel Leist, Costanza Rovida, Thomas HartungAbstract:For a long time, the discussion about Animal testing vs its alternatives centered on Animal welfare. This was a static warfare, or at least a gridlock, where life scientists had to take a position and make their value choices and hardly anyone changed sides. Technical advances have changed the frontline somewhat, with in vitro and in silico methods gaining more ground. Only more recently has the economic view begun to have an impact: Many Animal Tests are simply too costly, take too long, and give misleading results. As an extension and update to previous articles in this series written a decade ago, we reanalyze the economic landscape of especially regulatory use of Animal testing and this time also consider respective alternative Tests. Despite some ambiguity and data gaps, which we have filled with crude estimates, a picture emerges of globally regulated industries that are subject to stark geographic and sectorial differences in regulation, which determine their corresponding Animal use. Both Animal testing and its alternatives are industries in their own right, offering remarkable business opportunities for biotech and IT companies as well as contract research organizations. In light of recent revelations as to the reproducibility and relevance issues of many Animal Tests, the economic consequences of incorrect results and the reasons for still maintaining often outdated Animal test approaches are discussed.
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alternatives to Animal experimentation in basic research
ALTEX-Alternatives to Animal Experimentation, 2004Co-Authors: Franz P Gruber, Thomas HartungAbstract:: In contrast to Animal testing required by law to guarantee minimum safety standards for the licensing of drugs and chemicals, there are no regulations in basic research forcing scientists to perform Animal Tests. By (usually) free choice, questions are posed and hypotheses are examined which, in many cases, can only be answered by means of Animal Tests. Just as easily, different questions could be asked or different hypotheses could be examined which do not require Animal Tests. The only criterion for the choice of a topic is its relevance which cannot necessarily be judged in the short-term. Thus, it is up to the individual scientist to judge what is worth studying and therefore worth Animal consumption. The educated mind will consider ethical aspects of this choice. However, on the other hand, this decision is largely influenced by questions of efficacy or (in a negative sense) by the obstacles posed to an Animal consuming approach. Here, peer review and general attitude will strongly influence the methodology chosen. Availability and awareness of adequate in vitro techniques represent the prerequisites for the use of alternative methods. The least one can do in basic research is to avoid Tests which cause severe suffering to Animals, as is required in Switzerland and other European countries by binding ethical principles and guidelines. The increasing standard of approval and control procedures has improved the situation over the years. There are many examples of successful alternative methods in basic research. But, the application of such methods is in most cases limited to the laboratories in which they were developed, calling for technology transfer. Exceptions are procedures that are used worldwide, like the production of monoclonal antibodies, which instead of using the ascites mouse can also be performed in vitro with some good will. In these cases, commercialisation of the techniques has aided their spread within the scientific community. Sadly, many methods, even if published in the scientific literature, are little standardised and reproducible. The suggestion is put forward that publicly accessible databases should make available more detailed descriptions of methodologies. Due to limitations in space, many scientific journals cannot publish detailed methodological descriptions. However, nowadays a supplementary central deposit of methods could easily be linked to the respective article. In numerous cases though, there is simply a lack of will to change procedures to methods without Animal Tests or to pose questions differently in order to avoid the use of Animals or to reduce their number or, at least, to reduce stress. In other cases, researchers are simply not aware of the limitations of the Animal experiment as such. A thorough review of the validity of critical Animal experiments should be carried out and made available publicly. For example, many Animal experiments are dramatically "under-powered", i.e. carried out with groups that are too small to allow conclusions to be drawn from the outcome. This stands in marked contrast to in vitro experiments where replicate experiments usually represent no major problem. Since in vitro models are generally more prone to artefacts due to the numerous variables, e.g. of cell culture, the key requirement for their application is their validation and quality control. Guided by the experience from validation studies for alternative methods in toxicology, concepts of a Good Cell Culture Practice (GCCP) are currently being developed which aim to define minimum quality standards for in vitro techniques. This initiative aiming to increase quality must be complemented by a concept to systematically assess the relevance of the Tests in order to finally achieve an evidence-based biomedical research. A change in this direction is only possible if those public funds, which were previously assigned predominantly to alternatives to the Animal Tests required by law, are now channelled increasingly into developing those for basic research. A financial incentive is necessary to change procedures in basic research to Animal free procedures. Ethical considerations alone will bring little movement or change. It is unacceptable that, while numbers of Animal Tests decrease in development and notification of drugs and chemicals, they are increasing in basic research. Due to the central role of publishing scientific results, the key options for control are the respective rules of journals for the acceptance of articles. By demanding certain standards in the instructions for authors, e.g. of quality (GCCP), relevance and in case of Animal experiments proof that no alternative is available, pressure could be dramatically increased. It is suggested to hold a consensus conference of journals in the life sciences on this topic.
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ecvam s response to the changing political environment for alternatives consequences of the european union chemicals and cosmetics policies
Atla-alternatives To Laboratory Animals, 2003Co-Authors: Thomas Hartung, Susanne Bremer, Silvia Casati, Sandra Coecke, Raffaella Corvi, Salvador Fortaner, Laura Gribaldo, Marlies Halder, Pilar Prieto, E SabbioniAbstract:The European Centre for the Validation of Alternative Methods (ECVAM) has restructured its services by directly targeting the Animal Tests that need to be replaced. In view of the short time-lines ...