Early Social Enrichment Improves Social Motivation and Skills in a Monogenic Mouse Model of Autism, theOprm1^−/−Mouse

Abstract

Environmental enrichment has been proven to have positive effects on both behavioral and physiological phenotypes in rodent models of mental and neurodevelopmental disorders. In this study, we used mice lacking the µ-opioid receptor gene (Oprm1 −/−), which has been shown to have deficits in social competence and communication, to assess the hypothesis that early enrichment can ameliorate sociability during development and adulthood. Due to the immaturity of sensory-motor capabilities of young pups, we chose as environmental stimulation a second lactating female, who provided extra maternal care and stimulation from birth. The results show that double mothering normalized the abnormal response to maternal separation in Oprm1 −/− pups and increased social motivation in juveniles and adult knockout mice. Additionally, we observed that Oprm1 −/− mice act as less attractive social partners than wild types, which suggests that social motivation can be modulated by the stimulus employed. This experiment supports previous findings suggesting that early social environmental stimulation has profound and long-term beneficial effects, encouraging the use of nonpharmacological interventions for the treatment of social defects in neurodevelopmental diseases.

Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder

“…Our results indicate that raising Shank3 mutant mice in enriched environments has little effect on their behavior, which is somewhat surprising, given that environmental enrichment has been shown to alleviate behavioral phenotypes in a number of other rodent models of ASDs (Favre et al, ; Garbugino et al, ; Kerr et al, ; Kondo et al, ; Lacaria et al, ; Lonetti et al, ; Nag et al, ; Oddi et al, ; Restivo et al, ; Reynolds et al, ; Schneider et al, ; Yamaguchi et al, ). A summary of previous findings along with findings from the current study is provided in Table .…”

“…Numerous animal models have been created to tease apart the complex pathophysiology of ASD (Bey & Jiang, ; Hulbert & Jiang, ). One interesting finding from across various models is that housing rodents in an enriched environment, including more space and objects in which to interact and in some cases more rodents, prevents the expression of ASD‐like behavioral phenotypes (Favre et al, ; Garbugino, Centofante, & D'Amato, ; Kerr, Silva, Walz, & Young, ; Kondo et al, ; Lacaria, Spencer, Gu, Paylor, & Lupski, ; Lonetti et al, ; Nag et al, ; Oddi et al, ; Restivo et al, ; Reynolds, Urruela, & Devine, ; Schneider, Turczak, & Przewłocki, ; Yamaguchi et al, ). Although the type of enrichment and the developmental stages during exposure varied considerably, all these previous studies reported improvements on at least one behavioral outcome and seldom reported any adverse effects of enrichment.…”

Back-translating behavioral intervention for autism spectrum disorders to mice with blunted reward restores social abilities

“…These improvements, though, rapidly faded when daily encounters ceased. In contrast, social enrichment produced partial but persistent beneficial effects on social abilities in Oprm1 −/− mice when provided from neonatal age 64 . Earlier training under the SI-NR condition may thus be required to obtain stable social improvements in these animals.…”

The Social Component of Environmental Enrichment Is a Pro-neurogenic Stimulus in Adult c57BL6 Female Mice

“…In this regard, both EE and SE induce recovery in various models of central nervous system injury (Berrocal et al, 2007; Gajhede Gram et al, 2015; Lajud et al, 2018). Moreover, EE increases AHN in mouse models of Down syndrome (Chakrabarti et al, 2011; Pons-Espinal et al, 2013), Alzheimer’s disease (Levi and Michaelson, 2007; Mirochnic et al, 2009; Rodriguez et al, 2011; Valero et al, 2011; Llorens-Martin et al, 2013; Marlatt et al, 2013), Huntington’s disease (Lazic et al, 2006), diabetes (Pamidi and Nayak, 2014), ischemia (Rojas et al, 2013), and chronic pain (Zheng et al, 2017), after cranial irradiation (Garbugino et al, 2016), and during physiological aging (Kempermann et al, 1998, 2002; Kempermann, 2008, 2015; Speisman et al, 2013). In contrast, early SE reverses social deficits in animal models of autism (Garbugino et al, 2016; Campolongo et al, 2018), Parkinson’s disease (Goldberg et al, 2012), and Fragile X syndrome (Oddi et al, 2015).…”