Prenatal Protein Malnutrition in the Rat Reduces Extracellular Norepinephrine in the Ventral Medial Prefrontal Cortex and Impairs Performance in Attentional Set Shifting

Abstract

Our research on the behavioral and neuroanatomical consequences of prenatal protein malnutrition (PPM) has focused on the prefrontal cortex (PFC) given clinical findings of deficits in executive function in a human population (Galler et al., 2012; Waber et al., 2014). Female rats were fed low protein (6% casein) or adequate protein (25% casein) diets for five weeks prior to mating and throughout gestation. At birth, litters were culled to eight pups and cross-fostered to well-nourished dams. At adulthood, males were tested in an attentional set shifting task (ASST, McGaughy et al., 2014). An additional group was tested in the ASST and then implanted with microdialysis probes bilaterally into the ventral medial PFC (vmPFC). Results from the ASST showed that malnourished rats took more trials on reversals than well-nourished rats. Microdialysis probes showed significantly lower levels of extracellular norepinephrine (NE) in the right vmPFC in malnourished rats, but no difference between groups in the left vmPFC. These data suggest that NE levels in right vmPFC normally contribute to ASST performance but that in the prenatally malnourished rats, reduction in NE may contribute to impaired ASST performance but individual differences within the malnourished group do not account for suggesting impairments in other systems as well. These data also suggest that prenatal protein malnutrition alters brain circuits in the two hemispheres in a different manner. Supported by NIH/MH 074811.