Maternal care of heterozygous dopamine receptorD4knockout mice:Differential susceptibility to early-life rearing conditions

The differential susceptibility hypothesis proposes that individuals who are more susceptible to the negative effects of adverse rearing conditions may also benefit more from enriched environments. Evidence derived from human experiments suggests the lower efficacy dopamine receptor D4 (DRD4) 7-repeat as a main factor in exhibiting these for better and for worse characteristics. However, human studies lack the genetic and environmental control offered by animal experiments, complicating assessment of causal relations. To study differential susceptibility in an animal model, we exposed Drd4+/− mice and control litter mates to a limited nesting/bedding (LN), standard nesting (SN) or communal nesting (CN) rearing environment from postnatal day (P) 2-14. Puberty onset was examined from P24 to P36 and adult females were assessed on maternal care towards their own offspring. In both males and females, LN reared mice showed a delay in puberty onset that was partly mediated by a reduction in body weight at weaning, irrespective of Drd4 genotype. During adulthood, LN reared females exhibited characteristics of poor maternal care, whereas dams reared in CN environments showed lower rates of unpredictability towards their own offspring. Differential susceptibility was observed only for licking/grooming levels of female offspring towards their litter; LN reared Drd4+/− mice exhibited the lowest and CN reared Drd4+/− mice the highest levels of licking/grooming. These results indicate that both genetic and early-environmental factors play an important role in shaping maternal care of the offspring for better and for worse

Pro-social preference in an automated operant two-choice reward task under different housing conditions:Exploratory studies on pro-social decision making

In this study, we aimed to develop a behavioral task that measures pro-social decision making in rats. A fully automated, operant pro-social two-choice task is introduced that quantifies pro-social preferences for a mutual food reward in a set-up with tightly controlled task contingencies. Pairs of same-sex adult Wistar rats were placed in an operant chamber divided into two compartments (one rat per compartment), separated by a transparent barrier with holes that allowed the rats to see, hear, smell, but not touch each other. Test rats could earn a sucrose pellet either for themselves (own reward) or for themselves and the partner (both reward) by means of lever pressing. On average, male rats showed a 60 % preference for the lever that yielded a food reward for both themselves and their partner. In contrast, females did not show lever preference, regardless of the estrous cycle phase. Next, the impact of juvenile environmental factors on male rat social decision making was studied. Males were group-housed from postnatal day 26 onwards in complex housing Marlau™ cages that provided social and physical enrichment and stimulation in the form of novelty. Complex housed males did not show a preference for the pro-social lever

Maternal care of heterozygous dopamine receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions

The differential susceptibility hypothesis proposes that individuals who are more susceptible to the negative effects of adverse rearing conditions may also benefit more from enriched environments. Evidence derived from human experiments suggests the lower efficacy dopamine receptor D4 (D

Effects of Maternal Deprivation and Complex Housing on Rat Social Behavior in Adolescence and Adulthood

Early life context and stressful experiences are known to increase the risk of developing psychiatric disorders later in life, including disorders with deficits in the social domain. Our study aimed to investigate the influence of early life environment on social behavior in a well-controlled animal model. To this end we tested the effects of maternal deprivation (MD) on rat social play behavior in adolescence and social interaction in adulthood. Additionally, we provided a stimulating environment during adolescence (complex housing) as a potential intervention to diminish the effects of early life stress. Male and female Wistar rats were deprived from their mother for 24 h on postnatal day 3 (PND 3) or were left undisturbed. Complex housing started 5 days after weaning and consisted of housing 10 same-sex conspecifics in large, two-floor MarlauTM cages until the end of the study. Social play behavior in adolescence was tested under different conditions (3 h vs. 24 h social isolation prior to testing). Maternally deprived males - but not females - showed a longer latency to play and a decreased total amount of social play behavior, after a 24 h isolation period. In adulthood, social discrimination was impaired in deprived male and female rats in the three-chamber social approach task. Complex housing did not moderate the effects of MD, but in itself induced a strong behavioral phenotype. Both complex housed males and females hardly displayed any play behavior after a 3 h isolation period. However, after 24 h of isolation, these animals showed shorter latencies to engage in social play behavior. Only complex housed males truly showed more social play behavior here, while showing less social interest in adulthood. We conclude that MD has mild negative effects on social behavior in adolescence and adulthood, which are not counteracted by complex housing. Complex housing induces a specific phenotype associated with rapid habituation; a lack of social play after short isolation periods, while increasing play behavior after a prolonged period of isolation in adolescence, and less social interest, paired with intact social discrimination in adulthood. In both early life settings, males seem to be more influenced by the early life environment compared to females

Effects of maternal deprivation and complex housing on rat social behavior in adolescence and adulthood

Early life context and stressful experiences are known to increase the risk of developing psychiatric disorders later in life, including disorders with deficits in the social domain. Our study aimed to investigate the influence of early life environment on social behavior in a well-controlled animal model. To this end we tested the effects of maternal deprivation (MD) on rat social play behavior in adolescence and social interaction in adulthood. Additionally, we provided a stimulating environment during adolescence (complex housing) as a potential intervention to diminish the effects of early life stress. Male and female Wistar rats were deprived from their mother for 24 h on postnatal day 3 (PND 3) or were left undisturbed. Complex housing started 5 days after weaning and consisted of housing 10 same-sex conspecifics in large, two-floor MarlauTM cages until the end of the study. Social play behavior in adolescence was tested under different conditions (3 h vs. 24 h social isolation prior to testing). Maternally deprived males - but not females - showed a longer latency to play and a decreased total amount of social play behavior, after a 24 h isolation period. In adulthood, social discrimination was impaired in deprived male and female rats in the three-chamber social approach task. Complex housing did not moderate the effects of MD, but in itself induced a strong behavioral phenotype. Both complex housed males and females hardly displayed any play behavior after a 3 h isolation period. However, after 24 h of isolation, these animals showed shorter latencies to engage in social play behavior. Only complex housed males truly showed more social play behavior here, while showing less social interest in adulthood. We conclude that MD has mild negative effects on social behavior in adolescence and adulthood, which are not counteracted by complex housing. Complex housing induces a specific phenotype associated with rapid habituation; a lack of social play after short isolation periods, while increasing play behavior after a prolonged period of isolation in adolescence, and less social interest, paired with intact social discrimination in adulthood. In both early life settings, males seem to be more influenced by the early life environment compared to females

Complex Housing, but Not Maternal Deprivation Affects Motivation to Liberate a Trapped Cage-Mate in an Operant Rat Task.

Early life environment influences the development of various aspects of social behavior, particularly during sensitive developmental periods. We studied how challenges in the early postnatal period or (early) adolescence affect pro-social behavior. To this end, we designed a lever-operated liberation task, to be able to measure motivation to liberate a trapped conspecific (by progressively increasing required lever pressing for door-opening). Liberation of the trapped rat resulted either in social contact or in liberation into a separate compartment. Additionally, a condition was tested in which both rats could freely move in two separate compartments and lever pressing resulted in social contact. When partners were not trapped, rats were more motivated to press the lever for opening the door than in either of the trapped configurations. Contrary to our expectations, the trapped configuration resulted in a reduced motivation to act. Early postnatal stress (24 h maternal deprivation on postnatal day 3) did not affect behavior in the liberation task. However, rearing rats from early adolescence onwards in complex housing conditions (Marlau cages) reduced the motivation to door opening, both in the trapped and freely moving conditions, while the motivation for a sucrose reward was not affected

Maternal Environment Influences Cocaine Intake in Adulthood in a Genotype-Dependent Manner

Background: Accumulating epidemiological evidence points to the role of genetic background as a modulator of the capacity of adverse early experiences to give rise to mental illness. However, direct evidence of such gene-environment interaction in the context of substance abuse is scarce. In the present study we investigated whether the impact of early life experiences on cocaine intake in adulthood depends on genetic background. In addition, we studied other behavioral dimensions associated with drug abuse, i.e. anxiety- and depression-related behaviors. Methodology/Principal Findings: For this purpose, we manipulated the maternal environment of two inbred mouse strains, the C57BL/6J and DBA/2J by fostering them with non-related mothers, i.e. the C3H/HeN and AKR strains. These mother strains show respectively high and low pup-oriented behavior. As adults, C57BL/6J and DBA/2J were tested either for cocaine intravenous self-administration or in the elevated plus-maze and forced swim test (FST). We found that the impact of maternal environment on cocaine use and a depression-related behavior depends upon genotype, as cocaine self-administration and behavior in the FST were influenced by maternal environment in DBA/2J, but not in C57BL/6J mice. Anxiety was not influenced by maternal environment in either strain. Conclusions/Significance: Our experimental approach could contribute to the identification of the psychobiological factor

The added value of rodent models in studying parental influence on offspring development:Opportunities, limitations and future perspectives

Over the past decades, the influence of parental care on offspring development has been a topic of extensive research in both human and animal models. Rodent models offer several unique advantages over human studies, allowing for higher levels of environmental control, exploration of interventions, genetic control and examination of underlying neurobiological mechanisms in greater spatiotemporal detail. Although exploitation of these opportunities has led to increased understanding of the neurobiological mechanisms underlying susceptibility to the early-life environment, translation of results to human parenting and child development appears to be challenging. Attuning animal models to the human situation and application of novel structural and functional techniques is therefore of crucial importance to reduce the gap between rodent and human research