Intrauteruterine growth restriction increases tyrosine hydroxylase expression and propensity for addiction in low birth weight rats (1107.9)

Abstract

Obesity is an epidemic of growing concern. Much research has focused on the roles of hypothalamic feeding peptides in energy balance and how these are affected by gestational programming, the impact of the intrauterine environment on adult physiology. Gestational programming may also affect the mesolimbocortical pathway, which projects from the ventral tegmental area (VTA) to the nucleus accumbens and prefrontal cortex in the brain and comprises a general reward system that reinforces natural behaviors such as eating, drinking, and sexual activity. Since low birth weight (LBW) humans tend to exhibit both obesity and a propensity toward addiction, we hypothesized that lack of maternal nutrition may cause baseline changes in dopaminergic activity that lead to perturbations in ingestive behavior. We utilized a traditional rat model of intrauterine growth restriction by placing dams on a 50% food‐restricted diet during the latter half of pregnancy. Offspring had significantly lower birth weights (5.6±0.08g vs. 6.5±0.06g, p<0.01) and significantly higher tyrosine hydroxylase (TH) immunoreactivity in the VTA than controls (159±19 vs. 454±88 A.U., p<0.05), suggesting that they would be more sensitive to rewarding stimuli. Therefore, we examined sucrose consumption in these animals over a 24 hour period and in a limited access paradigm where animals received 10% sucrose for 90 minute intervals. LBW offspring consumed significantly more (29±2ml vs. 23±1ml, p<0.05) when given limited access to sucrose. This suggests that LBW offspring increase ingestive behaviors when given limited access to substances with rewarding properties. Consequently, the dopaminergic reward system deserves closer examination to determine its role in LBW‐related obesity. Grant Funding Source: Supported by APS UGSRF Fellowship