Adolescent social isolation changes social recognition in adult mice

Abstract

Rearing in social isolation has profound effects on several aspects of behavior in adult rodents. However, little is known about effects of social stress on social behavior in these animals. In the present study, we examined social recognition in mice of both sexes that were individually housed from 30 days of age until testing at approximately 80 days of age, individually housed from day 30 until day 60, followed by group housing from day 60 until testing at around 80 days of age and in control mice that were group housed throughout experiment. A standard social recognition test was performed with ovariectomized female conspecifics introduced into the home cage of tested mice for 1 min, eight consecutive times with 9 min breaks between tests, and in the ninth test, new, unfamiliar females were introduced. The time spent investigating stimulus mice during each of the nine tests was recorded. Group housed male and female mice showed strong pattern of social learning, whereas mice reared in isolation from day 30 until testing did not show evidence of social recognition. Interestingly, mice reared in isolation from 30 until 60 days of age and then group housed again, also showed reduced ability for social learning in comparison to the controls housed in groups through the entire period. These results therefore show that social isolation has a profound effect on social behavior in mice, and that even isolation for a limited period can produce lasting behavioral deficits.

Introduction

Early life stress can have long lasting deleterious effects on brain development and consequently on behavior in adult life [1]. Rearing in isolation either in infancy or in adolescence can produce severe behavioral consequences in adult life in rodents that are social animals by nature [2]. Such studies provide for better understanding of animal behavior and may have implications for human behavior and psychiatric disorders where social isolation is a contributing factor [1].

Mice and rats are social mammals living in large social groups in natural conditions [3], [4]. In laboratory conditions, however, males are sometimes housed individually to prevent intermale aggression, or unwanted mating if males and females would be housed together. Therefore, males (and even females) that have been used in behavioral testing are sometimes housed individually [5]. Unfortunately, such studies do not account for possible effects of social isolation on the outcome of behavioral testing. This is a potential problem because previous studies have shown that rearing in social isolation during the pubertal period can lead to hyperactivity and reduced habituation, reduced novel object recognition, and reduced floating time in forced swim tests. Interestingly, the effects on anxiety-like behavior are somewhat conflicting since social isolation decreased anxiety-like behavior assessed by elevated plus maze testing, but increased anxiety-like behavior in light–dark field testing in mice; and similar effects of social isolation have been reported for rats [6], [7], [8], [9]. Although the molecular mechanisms that lead to these behavioral deficits are mostly unknown, several studies have shown that social isolation directly affects brain development in juvenile rodents. Rearing in isolation has been reported to result in reductions of medial prefrontal cortex volume [10], cytoskeletal alterations in hippocampus [11] and changes in CREB expression and dopamine and serotonin turnover in different parts of the brain [6], [12].

Social recognition is critical for establishing and maintaining social structures in groups of animals living together. Tests for social recognition were first described by Thor and Holloway [13] and are based on monitoring the time that tested animals spend investigating conspecifics introduced multiple times into the cages of tested animals. In rats and mice, the time of investigation normally decreases with exposure to the same animal, and is increased upon exposure to novel unfamiliar animals, usually to the time as observed during the first exposure to the novel animal [5]. Interestingly, social recognition is usually sexually dimorphic with the reduction in time during the test with same animal being more prominent in males than in females [14], [15]. The influence of social isolation on performance in social recognition tests has not been thoroughly investigated. Recently, Zhao et al. reported abnormalities in social recognition in male rats, housed individually [16], but we are not aware of any reports concerning the effect of social isolation on social recognition in mice of both sexes, and particularly whether social isolation for a limited time period could have a lasting effect on social learning. The present study, therefore, examined social recognition in mice of both sexes that were reared in groups or in isolation from day 30 (beginning of puberty) until testing or for a limited period of time to explore whether social isolation could cause long-lasting alterations in murine social behavior.