Inter‐individual maternal care received and genotype interactions affect dopaminergic phenotypes in female rat offspring

Abstract

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.

Dopamine Genotype Interacts with Inter-Individual Licking Received on Later-Life Licking Provisioning in Female Rat Offspring

“…Studies in mice also show an important role of offspring genotype in maternal care received 17,18 . Findings from our group and others have shown effects of early-life inter-individual maternal care received on later life behavior [19][20][21][22][23] . We have also reported gene x environment interactions involved in some of these effects 20,21 .…”

“…Findings from our group and others have shown effects of early-life inter-individual maternal care received on later life behavior [19][20][21][22][23] . We have also reported gene x environment interactions involved in some of these effects 20,21 . For example, we recently reported an interaction between a dopamine receptor 2 (Drd2) single nucleotide polymorphism (rs107017253) and early-life average licking duration per bout (a proxy of maternal care quality) on strategy shifting and sucrose preference, two dopamine-related phenotypes 21 .…”

“…While a mediation analysis typically requires a significant direct association of the independent variable (early-life licking received) on the dependent outcome variable (maternal licking provisioning), we also hypothesized the sequence of causal variables a priori based on previous literature on the intergenerational transmission of maternal care 36 . We previously reported similar interactions between average licking received and the same Drd2 SNP in other DA-related behaviors 21 , but involving the A/A genotype, not A/G. It is possible that the nature of this interaction changes when the brain undergoes significant changes in the dopaminergic system, such as when a female rat is pregnant and preparing for postnatal care of her offspring 37,38 .…”

“…We have also reported gene x environment interactions involved in some of these effects 20,21 . For example, we recently reported an interaction between a dopamine receptor 2 (Drd2) single nucleotide polymorphism (rs107017253) and early-life average licking duration per bout (a proxy of maternal care quality) on strategy shifting and sucrose preference, two dopamine-related phenotypes 21 . Executive function measured by strategy shifting performance has previously been shown to be related to maternal care provisioning in human cohorts 24 .…”

“…The supernatant was collected and stored at -80°C. Dopamine (DA) and 3, 4-dihydroxyphenylacetic acid (DOPAC) levels were measured by high performance liquid chromatography (HPLC) as described by previous studies 21,29 . A BAS 460 MICROBORE-HPLC system with electrochemical detection (Bio-analytical Systems Inc., West Lafayette, IN) was used together with a Uniget C-18 reverse phase microbore column (#8949, Bio-analytical Systems Inc.).…”