Effects of single cage housing on stress, cognitive and seizure parameters in the rat and mouse pilocarpine models of epilepsy

Abstract

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 StatementMany 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.

On the interpretation of results obtained in singly housed animals

“…Remarkably, the seizure frequency is 16 times higher in isolated animals. 3 It is notable that we show that "epilepsy" and housing conditions are independent variables, which means that they produce effects independently from one another. This is the reason why the phenotype is so dramatic in socially isolated animals.…”

Consequences of housing conditions and interindividual diversity in rodent models of acquired epilepsy

“…7 Circulating testosterone levels in dominant males are, on average, five times as high as in subordinates, and so data variability in group-housed males may increase due to their dominance status and corresponding hormone levels. 7 Furthermore, because of animal welfare, the issue of group or single housing for rodents used in epilepsy studies is more complex than discussed by Manouze et al 1 Although group housing should be considered best practice, the removal | 2017 LÖSCHER of individual animals for surgery or behavioral testing can result in the disruption of an established social hierarchy. 8 Moreover, the appearance of disturbed behavior (aggressiveness or passivity) in experimental animals (eg, animals displaying overt seizures, or that are instrumented) may provoke hostile responses from cage-mates.…”

Cell assemblies in the cortico-hippocampal-reuniens network during slow oscillations

“…All experiments were performed in accordance with experimental guidelines approved by Aix-Marseille University Animal Care and Use Committee. All rats were group housed to avoid social isolation-induced stress (Manouze et al, 2019). A total of 18 rats were used in this study.…”