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 (pilo) 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.
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.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by impaired attention, impulsivity and hyperactivity. The “neonatal 6-hydroxydopamine” (6-OHDA) lesion is a commonly used model of ADHD in rat. However, a comprehensive assessment of ADHD‐like symptoms is still missing, and data in mouse remain largely unavailable. Our aim was to analyse symptoms of ADHD in the mouse neonatal 6‐OHDA model. 6‐OHDA mice exhibited the major ADHD‐like symptoms, i.e. hyperactivity (open field), attention deficit and impulsivity (five‐choice serial reaction time task). Further, the model revealed discrete co‐existing symptoms, i.e. anxiety‐like (elevated plus maze test) and antisocial (social interaction) behaviours and decreased cognitive functioning (novel object recognition). The efficacy of methylphenidate, a classical psychostimulant used in the treatment of ADHD, was also evaluated. A histological analysis further supports the model validity by indicating dopamine depletion, changes in cortical thickness and abnormalities in anterior cingulate cortex neurons. A principal component analysis of the behaviour profile confirms that the 6‐OHDA mouse model displayed good face and predictive validity. We conclude that neonatal dopamine depletion results in behavioural and morphological changes similar to those seen in patients and therefore could be used as a model for studying ADHD pathophysiological mechanisms and identifying therapeutic targets.
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