Lacking quality in research: Is behavioral neuroscience affected more than other areas of biomedical science?

Bespalov, Anton; Steckler, Thomas

doi:10.1016/j.jneumeth.2017.10.018

Cited by 22 publications

(18 citation statements)

References 30 publications

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“…Whatever the strategy used, success largely depends first on gathering reliable data from the literature. As for other biomedical subjects [72][73][74][75][76], lab-to-lab variability in routine transfection protocols in vitro (as depicted in Figure 1), that is, the lack of standard test procedures, has largely contributed to the huge number of inconsistent findings underpinning the reproducibility crisis. Indeed, scientists are flooded with data that are hard to digest, compare, and integrate into a clear view of how to design a transfectant with superior behavior.…”

Section: Nucleic Acid Description Site Of Action Applications/pathwaymentioning

confidence: 99%

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

et al. 2020

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Transfection by means of non-viral gene delivery vectors is the cornerstone of modern gene delivery. Despite the resources poured into the development of ever more effective transfectants, improvement is still slow and limited. Of note, the performance of any gene delivery vector in vitro is strictly dependent on several experimental conditions specific to each laboratory. The lack of standard tests has thus largely contributed to the flood of inconsistent data underpinning the reproducibility crisis. A way researchers seek to address this issue is by gauging the effectiveness of newly synthesized gene delivery vectors with respect to benchmarks of seemingly well-known behavior. However, the performance of such reference molecules is also affected by the testing conditions. This survey points to non-standardized transfection settings and limited information on variables deemed relevant in this context as the major cause of such misalignments. This review provides a catalog of conditions optimized for the gold standard and internal reference, 25 kDa polyethyleneimine, that can be profitably replicated across studies for the sake of comparison. Overall, we wish to pave the way for the implementation of standardized protocols in order to make the evaluation of the effectiveness of transfectants as unbiased as possible.

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Section: Nucleic Acid Description Site Of Action Applications/pathwaymentioning

confidence: 99%

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

et al. 2020

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“…classical block design. On occasion, this has led to issues of experiments being underpowered and concerns about overinterpretation and reproducibility of study outcomes (Kilkenny et al, 2009;Button et al, 2013;Bespalov and Steckler, 2018). The present five-choice and Go-NoGo studies were initially run using such a block design.…”

Section: Rationale For Study Designmentioning

confidence: 99%

“…Although each drug has been widely reported on 5-CSRTT performance by various groups (see subsequent references), an advantage of the present work is that each have been tested under equivalent test conditions (see Table 6 for Summary). This eliminates variations in environmental and precise test conditions used between labs, and that is often cited as a factor influencing robustness of behavioral research findings across labs (Bespalov et al, 2016;Voelkl and Würbel, 2016;Bespalov and Steckler, 2018). Measured over increasing dosage, the psychostimulants AMP and MPH elicit a continuum of behavioral and cognitive activation which transition from the beneficial to the detrimental (Grilly and Loveland, 2001;Wood et al, 2013;Berridge et al, 2012).…”

Section: Characterization Of Amp Mph Atx and Nic On Performancementioning

confidence: 99%

“…A second outcome has been to question the rigor and standards by which animal studies themselves have been conducted with calls for better study design and conduct, and ensuring studies are appropriately powered (Kilkenny et al, 2009;Kilkenny et al, 2010;van der Worp et al, 2010;Button et al, 2013;Bespalov et al, 2016;Bespalov and Steckler, 2018). A further development has been a recognition that psychiatric disorders typically consist of specific symptoms, or endophenotypes, that can extend across multiple diagnostic categories and represent discrete measurable entities (Castellanos and Tannock, 2002;Hyman and Fenton, 2003;Hasler et al, 2004;Robbins et al, 2012;Kozak and Cuthbert, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Amphetamine, Methylphenidate, Nicotine, and Atomoxetine on Measures of Attention, Impulsive Action, and Motivation in the Rat: Implications for Translational Research

Higgins

Silenieks²,

MacMillan³

et al. 2020

Front. Pharmacol.

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Amphetamine (AMP), methylphenidate (MPH), and atomoxetine (ATX) are approved treatments for ADHD, and together with nicotine (NIC), represent pharmacological agents widely studied on cognitive domains including attention and impulsive action in humans. These agents thus represent opportunities for clinical observation to be reinvestigated in the preclinical setting, i.e., reverse translation. The present study investigated each drug in male, Long Evans rats trained to perform either (1) the fivechoice serial reaction time task (5-CSRTT), (2) Go/NoGo task, or (3) a progressive ratio (PR) task, for the purpose of studying each drug on attention, impulsive action and motivation. Specific challenges were adopted in the 5-CSRTT designed to tax attention and impulsivity, i.e., high frequency of stimulus presentation (sITI), variable reduction in stimulus duration (sSD), and extended delay to stimulus presentation (10-s ITI). Initially, performance of a large (> 80) cohort of rats in each task variant was conducted to examine performance stability over repeated challenge sessions, and to identify subgroups of "high" and "low" attentive rats (sITI and sSD schedules), and "high" and "low" impulsives (10-s ITI). Using an adaptive sequential study design, the effects of AMP, MPH, ATX, and NIC were examined and contrasting profiles noted across the tests. Both AMP (0.03-0.3 mg/kg) and MPH (1-6 mg/kg) improved attentional performance in the sITI but not sSD or 10-s ITI condition, NIC (0.05-0.2 mg/kg) improved accuracy across all conditions. ATX (0.1-1 mg/kg) detrimentally affected performance in the sITI and sSD condition, notably in "high" performers. In tests of impulsive action, ATX reduced premature responses notably in the 10-s ITI condition, and also reduced false alarms in Go/NoGo. Both AMP and NIC increased premature responses in all task variants, although AMP reduced false alarms highlighting differences between these two measures of impulsive action. The effect of MPH was mixed and appeared baseline dependent. ATX reduced break point for food reinforcement suggesting a detrimental effect on motivation for primary reward. Taken

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“…Among the other factors, this can certainly be one of the major issues contributing to the current "reproducibility crisis" in basic research 15,16 . Moreover, the concerns have been expressed that the low quality of basic and pre-clinical studies (not limited to behavioral studies) 17 may have a direct relation to the failures in clinical trials 18,19 .…”

Section: Introductionmentioning

confidence: 99%

Experiments done in Black-6 mice: what does it mean?

Åhlgren

Võikar

2019

Lab Anim

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Low replicability of animal experiments is perceived as a major hurdle in the field of biomedicine. Attempts to enhance the replicability and to reduce the variability in basic research has led to a recommendation to use isogenic mice. The C57BL/6 strain has evolved as a gold standard strain for this purpose. However, the C57BL/6 mice are maintained as sub-strains by multiple vendors. Evidence exists that the subtle differences between these mouse lines have not been systematically investigated and are often ignored. In the present study, we characterized the female mice of two closely related sub-strains (C57BL/6J and C57BL/6N) from three vendors in Europe (Charles River Laboratories, Envigo, Janvier Labs) in a battery of behavioral tests. Our data show and confirm substantial behavioral differences between the C57BL/6J and C57BL/6N mice. Importantly, the sub-strain differences were largely affected by the origin of animals, as a significant effect of vendor or interaction between the sub-strain and vendor occurred in all tests. This work highlights the importance of adhering to precise international nomenclature in all publications reporting the animal experiments. Moreover, the generalization of research findings from a single mouse sub-strain can be seriously limited due to genetic drift and environmental variables at different vendors. However, generalizability can be enhanced by heterogenization of samples by including the animals of different substrains. These issues need to be seriously considered for improving reproducibility, replicability and translational potential of the mouse models.

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Lacking quality in research: Is behavioral neuroscience affected more than other areas of biomedical science?

Cited by 22 publications

References 30 publications

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

Characterization of Amphetamine, Methylphenidate, Nicotine, and Atomoxetine on Measures of Attention, Impulsive Action, and Motivation in the Rat: Implications for Translational Research

Experiments done in Black-6 mice: what does it mean?

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