Exposure to high fat during early development impairs adaptations in dopamine and neuroendocrine responses to...

Perturbations in the perinatal environment have been shown to significantly alter mesolimbic dopamine (DA) and hypothalamic-pituitary-adrenal (HPA) responses to stressors in adulthood. We have previously demonstrated that adult offspring exposed to high fat during the last week of gestation and throughout lactation display permanent alterations in mesolimbic DA function and behavior. The goal of the present study was to investigate nucleus accumbens (NAc) DA and HPA responses to acute and repeated stress in high fat exposed (HFD, 30% fat) and control (CD, 5% fat) offspring. Using microdialysis to monitor extracellular DA, we report that adult HFD offspring show an enhanced NAc DA response to acute tail-pinch compared to CD offspring. With repeated tail-pinch, the response of the HFD animals remains unchanged while CD offspring exhibit a sensitized DA response. The pattern of the DA response to both acute and repeated stress is also significantly altered by early diet exposure with an earlier peak and faster return to baseline levels in CD compared with HFD offspring. Similarly, neuroendocrine adaptations to repeated tail-pinch are observed in CD animals, but not in HFD animals. While controls display a habituated adrenocorticotropic hormone (ACTH) response to repeated tail-pinch, and an exacerbated ACTH response to a novel stressor, this effect was not observed in the HFD offspring. Together, our data demonstrate that exposure to high fat during early development impairs adaptations in NAc DA and HPA responses usually observed with repeated stress.