Neonatal overfeeding alters adult anxiety and stress responsiveness

The neonatal nutritional environment is critical for programming the systems regulating body weight, and an inappropriate nutritional environment in early life can lead to overweight or obesity later on. In this study we demonstrate that changes to the neonatal nutritional environment, induced by changing the litter size in which the animal is raised, can alter not only body weight into adulthood, but also anxiety behaviours and stress responsiveness. These effects appear to be somewhat sex-dependent, affecting female rats more strongly than males. Thus, Wistar rats raised in small litters, where they have greater access to their mothers' milk, weigh more in adulthood than those raised in large litters. Females from these small litters show enhanced exploratory behaviour and reduced anxiety in the elevated plus maze, entering the open arms more often. They also display enhanced central responses to restraint stress including greater activation of the paraventricular nucleus of the hypothalamus and paraventricular nucleus of the thalamus, possibly indicating that the changes we see are related to enhanced arousal. Thus, while neonatal litter size affects long-term body weight regulation, it can also alter long-term activity, anxiety and stress responsiveness, and the degree to which it does so appears to be sex-dependent.