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

Genes Brain Behav. 2020 Sep;19(7):e12655. doi: 10.1111/gbb.12655. Epub 2020 Jun 15.


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.

Keywords: animal model; communal nesting; differential susceptibility; dopamine receptor D4; early-life adversity; gene-environment interaction; intergenerational transmission; limited bedding/nesting; maternal care; puberty onset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Female
  • Genotype
  • Heterozygote
  • Male
  • Maternal Behavior*
  • Mice
  • Mice, Inbred C57BL
  • Nesting Behavior*
  • Receptors, Dopamine D4 / genetics*
  • Social Environment*


  • Drd4 protein, mouse
  • Receptors, Dopamine D4