title: Repeated measurements of motor activity in rats in long-term toxicity studies.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  There was no overall difference between strains, and only minor differences were 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 between Wistar 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.
authors.affiliation: CiToxLAB Scantox A/S, Hestehavevej 36A, Ejby, DK-4623 Lille Skensved, Denmark. Electronic address: vg@dk.citoxlab.com.
authors.forename: V
authors.initials: V
authors.lastname: Golozoubova
authors.affiliation: CiToxLAB Scantox A/S, Hestehavevej 36A, Ejby, DK-4623 Lille Skensved, Denmark.
authors.forename: T K
authors.initials: TK
authors.lastname: Brodersen
authors.affiliation: CiToxLAB Scantox A/S, Hestehavevej 36A, Ejby, DK-4623 Lille Skensved, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Klastrup
authors.affiliation: CiToxLAB Scantox A/S, Hestehavevej 36A, Ejby, DK-4623 Lille Skensved, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Oksama
authors.affiliation: CiToxLAB Scantox A/S, Hestehavevej 36A, Ejby, DK-4623 Lille Skensved, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Løgsted
authors.affiliation: CiToxLAB Scantox A/S, Hestehavevej 36A, Ejby, DK-4623 Lille Skensved, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Makin
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D012462:Saline Solution, Hypertonic
keywords: Behavioural test battery; Open field test; Regulatory toxicology study; Safety pharmacology endpoints