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

INTRODUCTION: 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. RESULTS AND DISCUSSION: 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.

Growth, composition and eating quality of Longissimus dorsi from young bulls fed the ß-agonist cimaterol at consecutive developmental stages.

The objective was to investigate the effect of the ß-adrenergic agonist, cimaterol, on gain, composition and meat quality of primerib (M. longissimus dorsi) from Friesian young bulls slaughtered at different developmental stages. Twelve pairs of monozygotic twins were allocated to three liveweight (LW) groups (162, 299 and 407 kg, respectively). Within each pair, one animal was given 0·056 mg cimaterol per kg LW for 90 days, while the other served as a control. Cimaterol treatment increased the estimated gain and the weight of primerib by 55 and 20%, respectively (both P < 0·001), and lean and protein content of the longissimus dorsi muscle by 26 and 25%, respectively (both P < 0·001), and concomitantly reduced fat content of primerib by 16% (P < 0·01) and intramuscular fat in longissimus dorsi by 36% (P < 0·001). Cimaterol treatment reduced total collagen content (P < 0·02), but not collagen solubility (P > 0·55). Meat colour was slightly lighter (lightness, P < 0·06), but pH(24) and pH(final) was not affected by cimaterol. Cimaterol increased Volodkevich shear force values (P < 0·001). In general, the effect of cimaterol on meat quality characteristics was evident in all three LW groups, and LW only affected percent fat in primerib, intramuscular fat content in longissimus dorsi, meat colour and absolute contents of protein, fat and bone.