Effects of “Junk‐Food” on Excitatory Transmission and NMDA Receptor Subunit Expression in the NAc of Females

Abstract

Eating diets high in fats and sugars (i.e., “junk‐food”) produces alterations in the function of brain regions like the nucleus accumbens (NAc) that promote food‐seeking and over‐eating. For example, consumption of “junk‐food” increases the expression and function of high conductance calcium permeable AMPA receptors (CP‐AMPARS) in the NAc of obesity‐prone, but not obesity‐resistant male rats. These alterations persist for up to 30 days after initial “junk‐food” exposure. In addition, blockade of CP‐AMPARs within the NAc prevents enhanced food‐seeking in obesity‐prone rats. Thus, obesity‐prone rats are more sensitive to diet‐induced enhancements in NAc glutamatergic transmission that promote food‐seeking. However, whether similar experience‐induced alterations occur in females is unknown. Therefore, the goal of the studies presented here is to determine the effects of “junk‐food” on NAc glutamate receptor expression and function in females. Males were included for comparison and to replicate initial findings described above. Rats were given the “junk‐food” diet (10 days) followed by a return to ad lib standard chow for 14 days (i.e., “junk‐food” deprivation) in order to examine long‐lasting effects. Controls remained on standard chow throughout. Biotinylation or BS3 crosslinking followed by western blotting was then used to measure changes in the expression of AMPAR and NMDA receptor (NMDAR) subunits. In addition, whole‐cell patch clamp recordings from ex vivo brain slices were used to measure effects on AMPAR and NMDAR‐mediated transmission. Furthermore, the estrus cycle was monitored throughout and recordings were conducted in the metestrus/diestrus phase of the cycle. For biochemical studies, post hoc analyses are used to assess potential effects of the cycle on protein expression. In males, we found increases in GluA1, but not GluA2 surface expression and enhanced CP‐AMPAR‐mediated transmission following “junk‐food” consumption, replicating previous results. However, in females no effects on GluA1 or GluA2 surface expression or on AMPAR‐mediated transmission (CP‐AMPARs or non‐CP‐AMPARs) were found. However, there was a “junkfood” induced increase in the AMPA/NMDA ratio in females that was due to a reduction in NMDAR‐mediated transmission in the absence of any change in AMPAR‐mediated transmission. Thus, initial results show that there are sex differences in “junk‐food” induced alterations in CP‐AMPARs, and suggest a reduction in NMDA‐mediated transmission in females. Ongoing studies are examining effects of “junk‐food” on NMDAR subunit expression (GluN1, GluN2, GluN3). This will provide insights into which NMDAR populations may be affected. Together, these data shed light on potential sex specific mechanisms by which “junkfood” diet alters NAc function.Support or Funding InformationNIH R01 DK106188 (CRF)NIH F99 NS108549 (YAC)