Screening Approaches to Neurotoxicity: A Functional Observational Battery

1989 ◽  
Vol 8 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Virginia Clayton Moser

Observational tests to assess the behavioral and neurologic integrity of laboratory rats have been advanced for use in the primary screening of chemicals to detect neurotoxic potential. To examine the use of such an approach, we are systematically using a functional observational battery (FOB) to characterize known neurotoxicants and to assess its selectivity, reliability, specificity, and sensitivity. Our FOB is a series of tests that includes home cage and open field observations, neuromuscular and sensorimotor tests, and physiologic measures. Described in this article are the compounds we have tested to date and how the data have been integrated to produce a profile of effects for each. We have found the FOB to be sensitive to a variety of neurotoxicants, whose effects can be distinguished using a type of profile analysis as illustrated herein. This research effort provides important information about both the execution and the interpretation of FOB studies.

2016 ◽  
Vol 86 (1-2) ◽  
pp. 36-47 ◽  
Author(s):  
Imen Dridi ◽  
Nidhal Soualeh ◽  
Torsten Bohn ◽  
Rachid Soulimani ◽  
Jaouad Bouayed

Abstract.This study examined whether perinatal exposure to polluted eels (Anguilla anguilla L.) induces changes in the locomotor activity of offspring mice across lifespan (post-natal days (PNDs) 47 – 329), using the open field and the home cage activity tests. Dams were exposed during gestation and lactation, through diets enriched in eels naturally contaminated with pollutants including PCBs. Analysis of the eel muscle focused on the six non-dioxin-like (NDL) indicator PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153 and 180). Four groups of dams (n = 10 per group) received either a standard diet without eels or eels (0.8 mg/kg/day) containing 85, 216, or 400 ng/kg/day of ϵ6 NDL-PCBs. The open field test showed that early-life exposure to polluted eels increased locomotion in female offspring of exposed dams but not in males, compared to controls. This hyperlocomotion appeared later in life, at PNDs 195 and 329 (up to 32 % increase, p < 0.05). In addition, overactivity was observed in the home cage test at PND 305: exposed offspring females showed a faster overall locomotion speed (3.6 – 4.2 cm/s) than controls (2.9 cm/s, p <0.05); again, males remained unaffected. Covered distances in the home cage test were only elevated significantly in offspring females exposed to highest PCB concentrations (3411 ± 590 cm vs. 1377 ± 114 cm, p < 0.001). These results suggest that early-life exposure to polluted eels containing dietary contaminants including PCBs caused late, persistent and gender-dependent neurobehavioral hyperactive effects in offspring mice. Furthermore, female hyperactivity was associated with a significant inhibition of acetylcholinesterase activity in the hippocampus and the prefrontal cortex.


Author(s):  
Алина Викторовна Свиридова ◽  
Дарья Сергеевна Николенко ◽  
Мария Владимировна Абрамян ◽  
Владимир Вячеславович Алексеев

В работе представлены выявленные изменения поведения крыс при проведении эксперимента «Открытое поле» с хроническим воздействием на различные анализаторы крыс. Предположен адаптивный характер полученных результатов, связанный со стрессовой ситуацией при воздействии на органы чувств крыс. The paper presents the revealed changes in the behavior of rats during the "Open Field" experiment with chronic exposure to various rat analyzers. The adaptive nature of the results obtained is assumed to be associated with a stressful situation when exposed to the sensory organs of rats.


2020 ◽  
Author(s):  
Christoph Schrank

&lt;p&gt;About 50 years ago, John Ramsay and colleagues established the thorough foundation for the field-scale observational and mathematical description of the structures, deformation, and kinematics in ductile shear zones. Since then, these probably most important instabilities of the ductile lithosphere enjoyed an almost explosive growth in scientific attention. It is perhaps fair to say that this tremendous research effort featured four main themes:&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;[1] The historic scientific nucleus &amp;#8211; quantification of shear-zone geometry, strain and associated kinematic history from field observations&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;[2] Qualitative and quantitative analysis of microphysical deformation mechanisms in the field and the laboratory&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;[3] Shear-zone rheology&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;[4] The development of physically consistent mathematical models for shear zones, mainly using continuum mechanics.&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;In concert, these four cornerstones of shear-zone research enabled tremendous progress in our understanding of why and how ductile shear zones form. So, what are some of the outstanding problems?&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;A truly comprehensive model for ductile shear zones must account for the vast range of length and time scales involved, each easily covering ten orders of magnitude, as well as the associated intimate coupling between thermal, hydraulic, mechanical, and chemical processes. The multi-scale and multi-physics nature of ductile shear zones generates scientific challenges for all four research themes named above. This presentation is dedicated to highlighting exciting challenges in themes 2, and 3 and 4.&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;In the microanalytical arena [2], the nano-scale is an exciting new frontier, especially when it comes to the interplay between metamorphism and ductile deformation. The nano-frontier can be tackled with new synchrotron methods. I showcase some applications to fossil shear-zone samples and discuss opportunities for in-situ experiments. In the domain of rheology [3], I present some simple experiments with strain-softening materials and field observations that support the notion: transient rheological behaviour is very important for shear localisation. In the modelling domain [4], some recent examples for the intriguing physical consequences predicted by new multi-physics and cross-scale coupling terms in ductile localisation problems are illustrated.&lt;/p&gt;


2021 ◽  
Vol 8 ◽  
Author(s):  
Amanda J. Barabas ◽  
Jeffrey R. Lucas ◽  
Marisa A. Erasmus ◽  
Heng-Wei Cheng ◽  
Brianna N. Gaskill

Aggression among group housed male mice continues to challenge laboratory animal researchers because mitigation strategies are generally applied at the cage level without a good understanding of how it affects the dominance hierarchy. Aggression within a group is typically displayed by the dominant mouse targeting lower ranking subordinates; thus, the strategies for preventing aggression may be more successful if applied specifically to the dominant mouse. Unfortunately, dominance rank is often not assessed because of time intensive observations or tests. Several correlates of dominance status have been identified, but none have been directly compared to home cage behavior in standard housing. This study assessed the convergent validity of three dominance correlates (urinary darcin, tube test score, preputial gland to body length ratio) with wound severity and rankings based on home cage behavior, using factor analysis. Discriminant validity with open field measures was assessed to determine if tube test scores are independent of anxiety. Cages were equally split between SJL and albino C57BL/6 strains and group sizes of 3 or 5 (N = 24). Home cage behavior was observed during the first week, and dominance measures were recorded over the second. After controlling for strain and group size, darcin and preputial ratio had strong loadings on the same factor, which was a significant predictor of home cage ranking showing strong convergent validity. Tube test scores were not significantly impacted by open field data, showing discriminant validity. Social network analysis revealed that despotic power structures were prevalent, aggressors were typically more active and rested away from cage mates, and the amount of social investigation and aggression performed by an individual were highly correlated. Data from this study show that darcin and preputial ratio are representative of home cage aggression and provide further insight into individual behavior patterns in group housed male mice.


2021 ◽  
Author(s):  
◽  
Emily Gay Patterson-Kane

<p>Public concern with the caging conditions of animals kept in laboratories led to research assessing the standard conditions of rats housed in New Zealand laboratories. A total of 113 rats were used in experiments of four basic types. The experiments presented in the first and second chapters assessed the behaviours of rats housed in enriched, standard and deprived conditions. The assessment procedures used were the emergence box, open field and Hebb William's maze as well as the T-maze and a range of operant procedures. The behaviour of rats housed in standard conditions for the emergence box, open field and maze were intermediate between the enriched and deprived rats, but more closely resembled that of the deprived rats. However, the deprived rats displayed no general cognitive deficits on procedures other than the Hebb William's maze, causing the validity of the maze in this context to be questioned. A more specific cognitive deficit relating to attention at the time of encoding was indicated. The thesis then moved from looking for behavioural damage to examining what conditions rats would prefer, and extending these findings using behavioural economics. The rats showed significant preferences for only a small number of cage modifications. They clearly preferred nesting boxes and shredded paper, and showed some preference for a larger group size of rats. The demand experiments demonstrated that the rats worked hardest for access to moderately sized environments with a group size of six. Therefore, the recommendation arising from the current study is that rats should be provided with nest boxes and paper, and provision should be made in the future for using cages suitable for groups of around six. There were also implications for the range of procedures used during the course of this investigation. The open field data suffers from an unstandardised procedure that probably allows a range of confounding variables to come into effect, specifically changes in activity across time. The preference tests (T-maze and continuous access) gave broadly equivalent data although there were small systematic differences in the results between the two tests which suggest they should be used together in order to cancel out these biases. The demand procedure is the pre-eminent option from a theoretical point of view but the detail of the procedure is in need of some development. The best way to achieve this progress would be through more extensive applied use of behavioural economics.</p>


Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 230-239 ◽  
Author(s):  
Sonoko Ogawa ◽  
Johnny Chan ◽  
Jan-Åke Gustafsson ◽  
Kenneth S. Korach ◽  
Donald W. Pfaff

Abstract Estrogens are known to increase running wheel activity of rodents primarily by acting on the medial preoptic area (mPOA). The mechanisms of this estrogenic regulation of running wheel activity are not completely understood. In particular, little is known about the separate roles of two types of estrogen receptors, ERα and ERβ, both of which are expressed in mPOA neurons. In the present study the effects of continuous estrogen treatment on running wheel activity were examined in male and female mice specifically lacking either the ERα (αERKO) or the ERβ (βERKO) gene. Mice were gonadectomized and 1 wk later implanted with either a low dose (16 ng/d) or a high dose (160 ng/d) of estradiol benzoate (EB) or with a placebo control pellet. Home cage running wheel activity was recorded for 9 d starting 10 d after EB implants. The same mice were also tested for open field activity before and after EB implants. In both female and male αERKO mice, running wheel activity was not different from that in corresponding wild-type (αWT) mice in placebo control groups. In both females and males it was increased by EB only in αWT, not αERKO, mice. In βERKO mice, on the other hand, both doses of EB equally increased running wheel activity in both sexes just as they did in βWT mice. Absolute numbers of daily revolutions of EB-treated groups, however, were significantly lower in βERKO females compared with βWT females. Before EB treatment, gonadectomized αERKO female were significantly less active than αWT mice in open field tests, whereas βERKO females tended to be more active than βWT mice. In male mice there were no effect of ERα or ERβ gene knockout on open field activity. Unlike its effect on running wheel activity, EB treatment induced only a small increase in open field activity in female, but not male, mice. These findings indicate that 1) in both sexes estrogenic regulation of running wheel activity is primarily mediated through the ERα, not the ERβ; and 2) hormone/genotype effects are specific to the type of locomotor activity (i.e. home cage running wheel activity and open field activity) measured.


2011 ◽  
Vol 10 (6) ◽  
pp. 673-682 ◽  
Author(s):  
A. Langford-Smith ◽  
M. Malinowska ◽  
K. J. Langford-Smith ◽  
G. Wegrzyn ◽  
S. Jones ◽  
...  

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