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Summary: Social isolation caused by housing animals alone increases stress and epilepsy in rodent models. The effects of social isolation may negatively impact the results of preclinical drug trials that use these animals.
The traditional method of housing mice and rats alone increases stress and worsens epilepsy, according to a new study published in eNeuro. The added stress could complicate results of pre-clinical drug trials.
Rodents are typically housed alone to prevent aggressive behaviors and simplify data collection. However, rats and mice are social animals, and isolation causes stress that could be a confounding factor in studies.
eNeuro Editor-in-Chief Christophe Bernard and colleagues examined how epileptic and healthy mice and rats fared in social or isolated housing conditions. They found that the isolated, healthy rodents displayed higher levels of stress and anxiety compared to the healthy rodents living in groups. Epileptic rodents also had more severe seizures when they were isolated, likely due to the increased stress of their environment.
These findings emphasize the need to recognize housing conditions as an important factor during experimental design and data analysis since increased stress could interfere with results. Because of this, previously unsuccessful drugs might have failed pre-clinical trials due to the increased stress of the rodents and could still be viable treatments.
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Source: SfN Media Contacts: Calli McMurray – SfN Image Source: The image is credited to Manouze et al., eNeuro 2019.
Original Research: Closed access “Effects of Single Cage Housing on Stress, Cognitive and Seizure Parameters in the Rat and Mouse Pilocarpine Models of Epilepsy”. H Manouze, A Ghestem, V Poillerat, M Bennis, S Ba-M’hamed, JJ Benoliel, C Becker and C Bernard. eNeuro. doi:10.1523/ENEURO.0179-18.2019
Effects of Single Cage Housing on Stress, Cognitive and Seizure Parameters in the Rat and Mouse Pilocarpine Models of Epilepsy
Many experimental approaches require housing rodents in individual cages, including in epilepsy research. However, rats and mice are social animals; and individual housing constitutes a stressful situation. The goal of the present study was to determine the effects of individual housing as compared to conditions maintaining social contact on stress markers and epilepsy. Control male mice socially housed during pretest and then transferred to individual cages for six weeks displayed anhedonia, increased anxiety and biological markers of stress as compared to pretest values or mice kept socially housed during six weeks. Pilocarpine-treated mice housed together showed increased levels of anhedonia, anxiety and stress markers as well as decreased cognitive performance as compared to the control group. The differences were more significant in pilocarpine-treated mice housed individually. Anxiety correlated linearly with cognitive performance and stress markers independently of the experimental conditions. In the male rat pilocarpine model, seizures were sixteen times more frequent in singly housed animals as compared to animals kept in pairs. Daily interactions with an experimenter in otherwise singly housed animals was sufficient to produce results identical to those found in animals kept in pairs. We propose that social isolation produces a severe phenotype in terms of stress and seizure frequency as compared to animals maintaining social contact (at least in these two models), a factor that needs to be taken into account for data interpretation, in particular for preclinical studies.
Significance Statement Many experimental approaches require housing rodents in individual cages, a stressful condition for social animals, even in an enriched environment context. Using the pilocarpine model of epilepsy in rats and mice, we report that singly housing animals develop a more severe phenotype in terms of stress and epilepsy as compared to animals maintaining social contact. We propose that social isolation adds a degree of complexity for the interpretation of data, which may be particularly relevant for preclinical studies.
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