High-Fructose Diet and Chronic Unpredictable Stress Modify Each Other’s Neurobehavioral Effects in Female Rats

A pervasive exposure to stressors and the consumption of fructose-containing beverages usually go hand-in-hand in everyday life. In contrast to their metabolic outcomes, their impact on the brain and behavior is still understudied. We examined the behavioral response to a novelty (open field test), the expression of biochemical indicators of neuronal activity (Egr1 and FosB/ΔFosB), the synaptic potentiation (CaMKIIα and pCaMKII^Thr286), the synaptic plasticity (synaptophysin, PSD95, gephyrin, and drebrin), and the GABAergic system (parvalbumin and GAD67), along with the glucocorticoid receptor (GR) and AMPK, in the medial prefrontal cortex of female Wistar rats subjected to liquid fructose supplementation (F), chronic unpredictable stress (S), or both (SF) over 9 weeks. The only hallmark of the F group was an increased expression of pCaMKII^Thr286, which was also observed in the S group, but not in the SF group. The SF group did not show hyperactivity, a decreased expression of FosB, or an increased expression of parvalbumin, as the S group did. The SF group, as with the S group, showed a decreased expression of the GR, although the basal level of corticosterone was unchanged. The SF group showed, as de novo marks, thigmotactic behavior, increased drebrin, and decreased gephyrin expression. These findings suggest that the long-term consumption of fructose, which itself has subtle neurobehavioral consequences, in combination with stress prevents some of its effects, but also contributes to novel outcomes not seen in single treatments.