Repeated measurements of motor activity in rats in long-term toxicity studies

• Published in: Journal of pharmacological and toxicological methods 2014-11, Vol.70 (3), p.241-245
• Main Authors: Golozoubova, V., Brodersen, T.K., Klastrup, S., Oksama, M., Løgsted, J., Makin, A.
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Behavioural test battery; Female; Male; Motor Activity - drug effects; Open field test; Rats; Rats, Sprague-Dawley; Rats, Wistar; Regulatory toxicology study; Safety pharmacology endpoints; Saline Solution, Hypertonic - administration & dosage; Saline Solution, Hypertonic - pharmacology; Time Factors; Toxicity Tests - methods
• ISSN: 1056-8719; 1873-488X
• DOI: 10.1016/j.vascn.2014.06.007

In the light of 3R (replace, reduce, refine) principles in animal experimentation and increased focus on delayed effects of treatment on central nervous system, the incorporation of behavioural tests into standard toxicology studies as a complement or substitution of a stand-alone safety pharmacology study appears very attractive, but poses some challenges. In the present study, we evaluated the results of an open field test (standard part of the behavioural test batte- ries) incorporated into the 3-month regulatory toxicology study. The study was performed in two rat strains most commonly used in toxicology studies (Wistar and Sprague Dawley (SprD)). Open field test was performed according to the standard protocol for stand-alone behavioural test (modified Irwin test) before the start of treat- ment (Day-7, “naïve” animals), on Day 2, inWeek 6 and inWeek 13 of treatment with saline. There was no overall difference between strains, and onlyminor differenceswere detected at the individual time points. With regard to time effect, the average values for most of the parameters were comparable throughout the study but individual variability in the performance in the arena was increased at repeated measurements compared to the start. In conclusion, performance in the open field arena did not differ principally betweenWistar and SprD rats of both genders. However, individual variability in the behaviour in the open field arena increased with time. This has clear implications for deciding the appropriate group size for this type of study and has to be taken into account in the design of a toxicology study with integrated safety pharmacology endpoints.