Repeated “Day 1” FOB testing in ICH S7A safety assessment protocols: The influence of within- and between-session learning

Gauvin, David V.; Zimmermann, Zachary J.; Dalton, Jill A.; Baird, Theodore J.

doi:10.1016/j.vascn.2017.02.018

Cited by 9 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Behavior tests for small animals such as mice and rats have been developed mainly as screening tests for general safety of new drugs [29, 30, 31]. The set of behavior tests designated as functional observational battery can test physical and mental status in mice and rats [23, 24, 25, 26, 27, 28]. Some tests in functional observational battery certainly require the vision to be performed correctly [33].…”

Section: Discussionmentioning

confidence: 99%

“…Some tests in functional observational battery certainly require the vision to be performed correctly [33]. We chose visual-forelimb placing response and landing hind limb foot splay test in the menu of functional observational battery [23, 24, 25, 26, 27, 28] to test the vision of rats in this study. Operant-conditioning lever-press response test is dependent on visual response to on-and-off of a lamp [29, 30, 34].…”

Section: Discussionmentioning

confidence: 99%

“…Visual forelimb-placing response and landing foot splay were tested at three time points: 4 weeks of the age (before surgery), 9 weeks of the age (2 weeks after film implantation), and 11 weeks of the age (4 weeks after film implantation) [22, 23, 24, 25, 26, 27, 28]. As visual placing response, with the tail of a rat was held up, the rat was neared to the flat surface of a table from about 15 cm (Fig.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Vision evaluation by functional observational battery, operant behavior test, and light/dark box test in retinal dystrophic RCS rats versus normal rats

Matsuo

Uchida

Yamashita

et al. 2019

Heliyon

View full text Add to dashboard Cite

Background Vision plays a key role in some behavior tests for rats. Okayama University-type retinal prosthesis (OUReP) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. This study aims to assess vision in retinal dystrophic (RCS) rats, in comparison with normal rats, by selected behavior tests. We also examined whether the tests could detect vision changes in RCS rats with dye-coupled film implantation. Methods Data sets were 5 normal rats, 4 untreated RCS rats, 7 RCS rats with dye-coupled films implanted at the age of 7 weeks after excluding unsuccessful implantation at autopsy. Behavior tests chosen were landing foot splay and visual forelimb-placing response in the menu of functional observational battery, operant-conditioning lever-press response and light/dark box test. Results Normal visual placing response was significantly less frequent in untreated RCS rats at the age of 9 and 11 weeks, compared with normal rats ( P = 0.0027, chi-square test) while normal response was significantly more frequent at the age of 9 weeks in RCS rats with dye-coupled film implantation, compared with untreated RCS rats ( P = 0.0221). In operant-conditioning lever-press test, the correct response rate was significantly lower in untreated RCS rats than in normal rats at the age of 9 weeks ( P < 0.05, Tukey-Kramer test) while the rate was not significantly different between normal rats and RCS rats with dye-coupled film implantation. In light/dark box test, the time to enter dark box was significantly shorter in normal rats, compared with untreated RCS rats or RCS rats with dye-coupled film implantation ( P < 0.05, Tukey-Kramer test). Conclusions Behavior tests of functional observational battery, operant-conditioning lever-press response and light/dark box test discriminated vision between normal rats and RCS rats. The visual placing response and operant-conditioning lever-press test might have sensitivity to detect vision recovery in RCS rats with OUReP implantation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Vision evaluation by functional observational battery, operant behavior test, and light/dark box test in retinal dystrophic RCS rats versus normal rats

Matsuo

Uchida

Yamashita

et al. 2019

Heliyon

View full text Add to dashboard Cite

show abstract

“…Also noteworthy is what happens within the 20 minutes that adults are able to maintain “sustained attention.” Cutting et al 118,119 reported a natural rhythm to human attention that requires the technician to experience a stimulus change every few seconds in order for maximum attention to be maintained. There is a vast and venerable literature on the deleterious effects of work shift duration on both attention and cognition (refer to the study by Gauvin et al 120 for references). “Mind wanderings” can be viewed as lapses of executive control as unrelated stimuli (external and internal) compete for attentional resources.…”

Section: Discussion/conclusionmentioning

confidence: 99%

CNS Safety Screening Under ICH S7A Guidelines Requires Observations of Multiple Behavioral Units to Assess Motor Function

Gauvin

Zimmermann

Dalton³

et al. 2019

Int J Toxicol

Self Cite

View full text Add to dashboard Cite

In the adoption of behavior as a critical end point in safety pharmacology and neurotoxicity screening, federal regulatory agencies have shifted the predominating scientific perspective from pharmacology back to the experimental analysis of behavior (psychology). Nowhere is this more evident than in tier I safety assessment of the central nervous system (CNS). The CNS and peripheral nervous system have multiple behavioral units of general activity. A complete picture of the motor control neural pathways cannot be measured by any one single approach. The CNS safety protocols under International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use S7A are required to be conducted in accordance with Good Laboratory Practices by trained technical staff. The CNS safety assessments necessitate the inclusion of a thorough and detailed behavioral analysis of home cage activity, the response to handling, and transportation to and observations within an open-field apparatus with ancillary measures of basal muscle tone, muscle strength, and tremor in a functional observation battery, as well as quantitative measurements of 3-dimensional activity in an automated photobeam arena. Cost-cutting initiatives or a radical application of the “reduce use” principle of the 3 Rs only jeopardize the spirit, intent, and predictive validity of tier I safety testing assays dictated by current drug safety guidelines.

show abstract

“…When a larger number of rats in each dose group are tested (n = 10-12), as is typical for neurotoxicity studies, evaluations may be restricted to time of peak effect or maximal blood levels based on prior pharmacokinetic studies. Whenever animals are tested multiple times in a day, considerations should be given for confounding influences such as habituation, decreased motivation, and fatigue of both the animals and the observers (Gauvin et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

The Irwin Test and Functional Observational Battery (FOB) for Assessing the Effects of Compounds on Behavior, Physiology, and Safety Pharmacology in Rodents

Mathiasen

Moser

2023

Current Protocols

View full text Add to dashboard Cite

The modified Irwin procedure or functional observational battery (FOB) can be used to achieve several goals. New chemical entities (NCEs) can be behaviorally screened for nervous system effects at a variety of doses to identify potential therapeutic uses and in the selection of appropriate doses for subsequent assays. NCEs can also be evaluated in the behavioral battery and compared with reference standards to assess liabilities in a new compound class, with an estimated therapeutic index being suggested by the doses used in comparison to therapeutic doses. For the assessment of neurotoxicology, the FOB is often used. The differences between the two assays are subtle. The procedures used are essentially the same, but when considering neurotoxicology, the FOB is often conducted using GLP guidelines, with more animals being used per group, and doses that are low enough to determine a no effect level and high enough to induce marked nervous system behaviors. © 2023 Wiley Periodicals LLC. Basic Protocol: The Irwin test and FOB for assessing the effects of compounds on behavior, physiology, and safety pharmacology in rodents

show abstract

Repeated “Day 1” FOB testing in ICH S7A safety assessment protocols: The influence of within- and between-session learning

Cited by 9 publications

References 51 publications

Vision evaluation by functional observational battery, operant behavior test, and light/dark box test in retinal dystrophic RCS rats versus normal rats

Vision evaluation by functional observational battery, operant behavior test, and light/dark box test in retinal dystrophic RCS rats versus normal rats

CNS Safety Screening Under ICH S7A Guidelines Requires Observations of Multiple Behavioral Units to Assess Motor Function

The Irwin Test and Functional Observational Battery (FOB) for Assessing the Effects of Compounds on Behavior, Physiology, and Safety Pharmacology in Rodents

Contact Info

Product

Resources

About