Enriched Early Life Experiences Reduce Adult Anxiety-Like Behavior in Rats: A Role for Insulin-Like Growth Factor 1

Abstract

Early life experiences can affect brain development, contributing to shape interindividual differences in stress vulnerability and anxiety-like behavior. In rodents, high levels of maternal care have long-lasting positive effects on the behavior of the offspring and stress response; postweaning rearing in an enriched environment (EE) or massage counteract the negative effects of maternal separation or prenatal stressors. We recentlyfoundthatinsulin-likegrowthfactor1(IGF-1)isakeymediatorofearlyEEormassageonbraindevelopment.Whetherearlyenrichment of experience can induce long-lasting effects on anxiety-like behavior and whether IGF-1 is involved in these effects is not known. We assessed anxiety-like behavior by means of the elevated plus maze in control adult rats and in adult rats subjected to early EE or to massage. We found that both EE and massage reduced adult anxiety-like behavior. Early IGF-1 systemic injections in rat pups reared in standard condition mimic the effects of EE and massage, reducing anxiety-like behavior in the adult; blocking early IGF-1 action in massaged and EE animals prevents massage and EE effects. In EE and IGF-1-treated animals, we assessed the hippocampal expression of glucocorticoid receptors (GRs) at postnatal day 12 (P12) and P60, finding a significantly higher GR expression at P60 for both treatments. These results suggest that IGF-1 could be involved in mediating the long-lasting effects of early life experiences on vulnerability/resilience to stress in adults.

The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning

“…By contrast, when dams were exposed to enrichment starting in the second half of gestation and continuing until postnatal day 12, offspring showed clear anxiolytic effects when tested in adult age. This anxiolytic effect was very similar to that observed following daily tactile stimulation of the pups until postnatal day 12 (Baldini et al 2013).…”

“…This is in contrast to some (Fox et al 2006;Baldini et al 2013), but not all studies (Magalhaes et al 2008;Magalhaes et al 2007). However, previous studies applied enrichment not only during lactation, but mostly in combination with gestational exposure.…”

Development of Anxiety-Like Behavior via Hippocampal IGF-2 Signaling in the Offspring of Parental Morphine Exposure: Effect of Enriched Environment

“…Early life EE could protect from, or remediate, the development of highly emotional and anxious responses in the rats exposed to stressors (Baldini et al, 2013;Francis et al, 2002). In the present study, adolescent EE evidently prevented the anxiety-like behaviors and dendritic retraction in the adult offspring of morphine-exposed rats, suggesting that early life EE can affect brain development and shape individual differences in anxiety and depression.…”

“…Early life environmental enrichment (EE) experience reduces the anxious phenotype in the rats exposed to stressors (Baldini et al, 2013;Francis et al, 2002). Therefore, we attempted to examine whether adolescent EE exposure could reverse the adult anxiety-like behavior in the offspring of parent animals exposed to morphine.…”

Adult Neurogenesis and Mental Illness

“…One study reported that housing pregnant dams in an enriched environment led to decreased anxiety-like behavior in adult offspring (Friske and Gammie, 2005). However, environmental enrichment for neonates and juvenile rodents had anxiolytic-and antidepressant-like effects on adult behavior in some studies (Baldini et al, 2013;Benaroya-Milshtein et al, 2004;Urakawa et al, 2013;Workman et al, 2011) but not others (Ishihama et al, 2010;Workman et al, 2011;Yildirim et al, 2012). Early-life wheel running also appears to have little effect on adult anxiety-like behavior (Ishikawa et al, 2014).…”