Behavioral testing and litter effects in the rabbit

Gümüş, Hikmet; Agyemang, Alex Adusei; Romantsik, Olga; Sandgren, Rebecca; Karlsson, Håkan; Gram, Magnus; Vallius, Suvi; Ley, David; Hove, Daniël L.A. van den; Bruschettini, Matteo

doi:10.1016/j.bbr.2018.02.032

Cited by 9 publications

(8 citation statements)

References 11 publications

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“…This is probably related to the fact that our protocol does not include a habituation session before the performance of the test. et al, 2019) and was in accordance to the observed range in (Gümüş et al, 2018). The object recognition task has also been performed in rabbits by different groups but some of them perform it using visual objects (Hoffman et al, 2010;Hoffman and Basurto, 2013).…”

Section: Resultssupporting

confidence: 70%

“…In our case, latency time (calculated as the time in seconds the animal needs to leave The mean (M) ± SD is presented for righting reflex, lineal movement, fore-hind paw distance, and olfaction time; the median (Mdn) and (Interquartile Range (IQR)) are presented for the rest of the endpoints. the familiar starting point and start exploring the open field) was above 100 s while in many other studies it was less than 50 s (Gümüş et al, 2018;Van der Veeken et al, 2019, 2020. This is probably related to the fact that our protocol does not include a habituation session before the performance of the test.…”

Section: Resultsmentioning

confidence: 87%

“…The object recognition task has also been performed in rabbits by different groups but some of them perform it using visual objects (Hoffman et al, 2010;Hoffman and Basurto, 2013). This testing modality is also considered valid for assessing object recognition (Gümüş et al, 2018). However, some studies report that rabbits may be able to distinguish a novel visual object after a 5 min inter-trial interval, but not after 20, 180, or 360 min (Hoffman et al, 2010;Hoffman and Basurto, 2013), whereas in our studies discrimination with olfactory stimuli is present after a 30 min inter-trial interval (Illa et al, 2013) and this result could be replicated by another group (Gümüş et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

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Protocols for the Evaluation of Neurodevelopmental Alterations in Rabbit Models In Vitro and In Vivo

et al. 2022

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The rabbit model is gaining importance in the field of neurodevelopmental evaluation due to its higher similarity to humans in terms of brain development and maturation than rodents. In this publication, we detailed 14 protocols covering toxicological relevant endpoints for the assessment of neurodevelopmental adverse effects in the rabbit species. These protocols include both in vitro and in vivo techniques, which also cover different evaluation time-points, the neonatal period, and long-term examinations at postnatal days (PNDs) 50–70. Specifically, the protocols (P) included are as follows: neurosphere preparation (GD30/PND0; P2) and neurosphere assay (P3), behavioral ontogeny (PND1; P4), brain obtaining and brain weight measurement at two different ages: PND1 (P5) and PND70 (P12), neurohistopathological evaluations after immersion fixation for neurons, astrocytes, oligodendrocytes and microglia (PND1; P6-9) or perfusion fixation (PND70; P12), motor activity (P11, open field), memory and sensory function (P11, object recognition test), learning (P10, Skinner box), and histological evaluation of plasticity (P13 and P14) through dendritic spines and perineuronal nets. The expected control values and their variabilities are presented together with the information on how to troubleshoot the most common issues related to each protocol. To sum up, this publication offers a comprehensive compilation of reliable protocols adapted to the rabbit model for neurodevelopmental assessment in toxicology.

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Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

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Protocols for the Evaluation of Neurodevelopmental Alterations in Rabbit Models In Vitro and In Vivo

et al. 2022

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“…Overall, it is important to include littermate correlations in the model when testing for dose effects when the littermates come from various litters (Lazic and Essioux, 2013). Several other studies, specifically a study conducted by Lazic and Essioux (2013) and a study on rabbits conducted by Gümüş et al (2018), have stated the importance of taking litter effects into account. If within litter correlations had been ignored in this study then the resulting pvalue may have been smaller than it should have been.…”

Section: Discussionmentioning

confidence: 99%

Convergence in Mixed Effects Logistic Regression Models

Churchill¹,

Kissling²

2019

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relations had been taken into account, the results would not have been significant. It has been previously reported that litter effects are a characteristic of dose response data and therefore, within-litter correlation must be included when conducting statistical analyses (Khera et al., 1989; Kupper et al., 1986). When the response is a continuous measure, adjusting for within-litter correlations is simple (Haseman and Kupper, 1979; Searle, 1971). To adjust for the within-litter correlation, when the continuous measure is normally distributed, a nested analysis of variance can be implemented (Haseman and Kupper, 1979). One paper states that adjusting for within-litter correlations is more difficult when the response is dichotomous and rare, such as the occurrence of less common tumors (Haseman and Kupper, 1979). Different statistical models have been created to include litter effect, with many undergoing constant improvement (Yamamoto and Yanagimoto, 1994). Some models must be altered to incorporate litter effect, including the dose response model (Khera et al., 1989). Haseman and Soares (1976) concluded that, when analyzing experiments that look at dichotomous fetal responses, binomial or Poisson models provide poor fits, as there is similarity between responses from the same litter (Kupper et al., 1986). It also seems that certain models such as multistage, multihit and probit, which multiple authors have used, tend to ignore litter effects (Scientific

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“…Secondly, their instinctive exploratory behavior with innate response to visual and olfactory stimuli makes the specie a perfect candidate for the behavioral neurosciences. Neurobehavioral assessments in rabbits have become widely accepted and the methodologies thereof have been greatly refined [34]. While animal models in behavioral neurosciences allows the study of brain-behavior relations under controlled conditions in living organisms, species-dependent behavior must be taken into account [35].…”

Section: Plos Onementioning

confidence: 99%

Earlier preterm birth is associated with a worse neurocognitive outcome in a rabbit model

et al. 2021

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Background Preterm birth (PTB) and particularly late preterm PTB has become a research focus for obstetricians, perinatologists, neonatologists, pediatricians and policy makers alike. Translational models are useful tools to expedite and guide clinical but presently no model exists that contextualizes the late PTB scenario. Herein we aimed to develop a rabbit model that echo’s the clinical neurocognitive phenotypes of early and late PTB. Methods Time mated rabbit does underwent caesarean delivery at a postconceptional age (PCA) of either 28 (n = 6), 29 (n = 5), 30 (n = 4) or 31 (n = 4) days, term = 31 d. Newborn rabbits were mixed and randomly allocated to be raised by cross fostering and underwent short term neurobehavioral testing on corrected post-natal day 1. Open field (OFT), spontaneous alteration (TMT) and novel object recognition (NORT) tests were subsequently performed at 4 and 8 weeks of age. Results PTB was associated with a significant gradient of short-term mortality and morbidity inversely related to the PCA. On postnatal day 1 PTB was associated with a significant sensory deficit in all groups but a clear motor insult was only noted in the PCA 29d and PCA 28d groups. Furthermore, PCA 29d and PCA 28d rabbits had a persistent neurobehavioral deficit with less exploration and hyperanxious state in the OFT, less alternation in TMT and lower discriminatory index in the NORT. While PCA 30d rabbits had some anxiety behavior and lower spontaneous alteration at 4 weeks, however at 8 weeks only mild anxiety driven behavior was observed in some of these rabbits. Conclusions In this rabbit model, delivery at PCA 29d and PCA 28d mimics the clinical phenotype of early PTB while delivery at PCA 30d resembles that of late PTB. This could serve as a model to investigate perinatal insults during the early and late preterm period.

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Behavioral testing and litter effects in the rabbit

Cited by 9 publications

References 11 publications

Protocols for the Evaluation of Neurodevelopmental Alterations in Rabbit Models In Vitro and In Vivo

Protocols for the Evaluation of Neurodevelopmental Alterations in Rabbit Models In Vitro and In Vivo

Convergence in Mixed Effects Logistic Regression Models

Earlier preterm birth is associated with a worse neurocognitive outcome in a rabbit model

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