Behavioral testing does not always yield similar results when replicated in different laboratories, and it usually remains unclear whether the variability in results is caused by different laboratory environments or different experimenters conducting the tests. In our study, we applied a systematic variation of housing conditions, laboratories and experimenters in order to test the influence of these variables on the outcome of behavioral tests. We wanted to know whether known effects of different housing conditions on behavior can be demonstrated regardless of the respective laboratory and experimenters. In this study, we compared the behavior of mice kept under enriched housing conditions with mice kept in unstructured cages regarding their exploratory, locomotor and anxiety-related behavior in the barrier test, in the open-field test and in the elevated plus-maze test. Experiments were conducted by six different persons in two different laboratories. In spite of an extensive protocol standardizing laboratory environment, animal maintenance and testing procedures, significant differences in absolute values between different laboratories as well as between different experimenters were noticed in the barrier test and in the elevated plus-maze test but not in the openfield test. However, with regard to the differences between enriched and unstructured housing conditions, overall consistent results were achieved by different experimenters in both laboratories. We conclude that the reliability of behavioral phenotyping is not challenged seriously by experimenter and laboratory environment as long as appropriate standardizations are met and suitable controls are involved.

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Alzheimer's disease (AD) is the most prevalent form of senile dementia worldwide. It is characterized by two major histological hallmarks: senile plaques, ie, extracellular deposits mainly consisting of ␤-amyloid (A␤), and neurofibrillary tangles, ie, intracellular accumulations of hyperphosphorylated tau protein.1 AD patients show progressing cognitive decline as well as noncognitive behavioral symptoms such as wandering, sleep disturbance, and physical aggression.2 There are various risk factors for AD including age, family history, or apolipoprotein E 4 genotype.3 Epidemiological studies additionally suggest that the amount of time spent on intellectual and physical activities negatively correlates with the extent of cognitive decline and even risk of developing AD. 4,5 Although it cannot be excluded that lower activity levels are early subclinical symptoms, one should consider them also as a risk factor. In line with this assumption is the use of cognitive training as a rehabilitative measure resulting in deceleration of dementia progress. However, the underlying molecular pathways are essentially unknown.In laboratory rodents cognitive, physical, and social stimulation can be regulated by altering housing conditions. It is well established that living in an enriched environment provided by additional structural or social stimuli may increase locomotor and exploratory activity, improve learning and memory performance, increase dendritic sprouting and synapse formation in the neocortex and hippocampus as well as neurogenesis in the dentate gyrus, 6 and affects behavioral, endocrinological, and immunological parameters.7 Environmental enrichment also facilitates recovery from acute brain lesions,

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