Effects of maternal care on the development of midbrain dopamine pathways and reward-directed behavior in female offspring

Variation within mesolimbic dopamine (DA) pathways has significant implications for behavioral responses to rewards, and previous studies have indicated long-term programming effects of early life stress on these pathways. In the current study, we examined the impact of natural variations in maternal care in Long Evans rats on the development of DA pathways in female offspring and the consequences for reward-directed behaviors. We found that tyrosine hydroxylase (TH) immunoreactivity in the ventral tegmental area was elevated by postnatal day 6 in response to maternal licking/grooming (LG), and that these effects were sustained into adulthood. Increased TH immunoreactivity was not found to be associated with altered epigenetic regulation or transcriptional activation of Th, but probably involved LG-associated changes in the differentiation of postnatal DA neurons through increased expression of Cdkn1c, and enhanced survival of DA projections through LG-associated increases in Lmx1b and brain-derived neurotrophic factor. At weaning, high-LG offspring had elevated DA receptor mRNA levels within the nucleus accumbens and increased conditioned place preference for a high-fat diet. In contrast, high-LG, as compared with low-LG, juvenile offspring had a reduced preference for social interactions with siblings, and haloperidol administration abolished group differences in conditioned place preference through a shift towards increased social preferences in high-LG offspring. The effects of maternal care on developing DA pathways and reward-directed behavior of female offspring that we have observed may play a critical role in the behavioral transmission of maternal LG from mother to daughter, and account for individual differences in the mesolimbic DA system.