In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multi-laboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies.

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Variation in effort to obtain rewards is a fact of mammalian everyday life. In this study, we assess how rats scale variable costs and benefits. Different groups of rats were trained in a T-maze to discriminate a high (three or five sugar pellets) from a low reward (one sugar pellet) arm. Subsequently barriers were introduced at the high and low reward side such that the overall long-term pay-off of the high reward arm finally became lower than that of the low reward arm. The data show that under different regimes of costs (climbing barriers) and benefits (number of rewards) of the two arms rats appear to shift their behaviour towards the better side according to a constant relative cost-benefit ratio between the arms. Such a ratio allows them to deal with variation in the (physical appearance of) costs and benefits and choose the best long-term option. © 2006 Elsevier B.V. All rights reserved.Keywords: Rats; Iowa gambling task; Sugar pellets; T-maze; Barriers; Cost-benefit assessment Variation in reward quality and magnitude is the rule rather than the exception for most organisms living under natural conditions. Therefore, both human and non-human animals trade off costs and benefits to optimise long-term behaviour [8,15]. As an example, it has been shown that humans choose the option with the best long-term pay-off in the Iowa Gambling Task, which contains moment-to-moment variation in costs (monetary losses) and benefits (monetary wins; 1). Effort to obtain rewards is another crucial factor in cost-benefit analyses. Several studies have been performed showing that animals assess costs and benefits of different options [6,7,[11][12][13]. These studies have shown that choice behaviour of animals is determined by the number of food items that can be obtained and the barriers that need to be crossed. However, it has not been assessed thus far how cost-benefit ratios of different options are directly compared and how moment-to-moment variation in effort and reward affects long-term choice behaviour when multiple options exist. Given the efficiency of behaviour in an environment that contains variation [8,15] it may be hypothesized that human and non-human animals scale variable costs and benefits according to a constant relative cost-benefit ratio. This allows them to deal with a * Corresponding author. Tel.: +31 30 2534373; fax: +31 30 2539227. E-mail address: R.vandenbos@las.vet.uu.nl (R. van den Bos).large number of costs and benefits, differing in actual (physical) appearance. We tested this in rats using a T-maze in which we introduced variation in rewards and effort.For this experiment, n = 17 Wistar rats (HsdCpb:WU, Harlan, The Netherlands) were used. All rats had already participated in another cost-benefit assessment experiment, which took place in a box different from the present experiment. They had been trained to discriminate arms differing in the proportion of sugar over quinine treated sugar pellets [2]. There was no evidence that this experiment had any effect on the present experiment. Al...

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