No abstract

Rat dams show natural variations in maternal care, licking and grooming (LG), that are associated with distinct behavioral and neural phenotypes in offspring. However, there has been limited research on the effects of differences in LG received by female pups and of variations in maternal care within the litter. Here, we investigated LG received by measuring active maternal care after pup retrieval of female offspring. We then examined locomotor activity, open field exploration, and restraint stress reactivity in adult female offspring. We also investigated the expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) and DNA methylation of the GR17 promoter in the hippocampus. High compared with low LG siblings and female offspring from high compared with low LG dams showed increased locomotor activity. High compared with low LG siblings also showed reduced anxiety behavior regardless of the overall level of LG received in the litter. Unexpectedly, both the lowest licked offspring from low LG litters and the highest licked offspring from high LG litters showed suppressed corticosterone (CORT) responses to stress. However, high LG offspring within litters also showed increased expression of the GR gene, which was negatively correlated with the CORT response to restraint. DNA methylation at 2 CpG sites within GR17 promoter was significantly higher in high LG offspring. These differences in the response to maternal care both within- and between-litters were distinct in part from previous reports of between litter effects, potentially a result of the sex studied or the methods used to observe maternal care.

Rat mothers exhibit natural variations in care and can shape offspring adult behaviour and their maternal care by affecting the dopaminergic system. We explored whether genotype and gene × environment interactions are involved in these processes in nulliparous female offspring. We assessed maternal licking/grooming toward individual female pups during the first week postpartum and dopamine‐related behaviour of the offspring in adulthood. Behaviours explored included strategy shifting, impulsive action and sucrose preference. Single nucleotide polymorphisms in the dopamine receptor 2, dopamine transporter and catechol‐O‐methyltransferase genes were examined in relation to offspring behaviour and baseline dopamine turnover in select brain regions. Dopamine receptor 2 (RS107017253) variation moderated, or interacted with, the relationship between early‐life licking received and behaviour. Specifically, offspring with the A/A genotype showed a significant correlation between early‐life licking received and behaviour. Offspring with the A/G and G/G genotypes did not show this relationship. Dopamine transporter gene variation affected offspring behaviour regardless of early‐life licking received. Our findings suggest that genotype can directly affect dopamine‐related behaviours and alter the sensitivity of offspring to the maternal environment. This could be informative on how maternal care is transmitted between generations of female offspring.

Rat dams differ naturally in the level of maternal care they provide to their offspring within the same litter. We explored possible mechanisms of differential maternal care focused on genetic variation. We examined single nucleotide polymorphisms in the glucocorticoid receptor, FK506-binding protein, and serotonin transporter genes in two separate cohorts, and the relationship between differential maternal care received, genotype, and offspring phenotype. Allelic variation in all three genes was significantly associated with levels of maternal care received by offspring and behavioral and endocrine stress responses in adulthood. Differences in pup behavior were also associated with allelic variation in these genes. Together, these results indicate that the dam/pup interaction is dynamic and implicate the genotype of the offspring in influencing the level of maternal care received. They further suggest that some genotypes may have a dampening effect on the impact of maternal care on stress-related phenotypes in adulthood.