Stress-induced reinstatement of palatable food seeking: Role of Dorsal Medial Prefrontal Cortex Dopamine D1-Family Receptors.

In humans, relapse to maladaptive eating habits during dieting is often provoked by stress. We adapted a drug reinstatement model to study the role of stress in relapse to food seeking (Nair et al. Prog. Neurobiol. 2009). In our model, the anxiogenic drug yohimbine, which causes stress-like responses in humans and laboratory animals, reliably reinstates food seeking. Here, we studied the role of the medial prefrontal cortex (mPFC) in yohimbine-induced reinstatement. We trained food-restricted rats to lever-press for 35% high-fat pellets every other day (9-15 3-h sessions). We then extinguished the food-reinforced operant responding for 10-16 days by removing the pellets. Subsequently, we tested the effect of systemic injections of yohimbine (0 or 2 mg/kg, i.p) on reinstatement of food seeking. Yohimbine-induced reinstatement was associated with strong Fos (a marker of neuronal activity) induction in the dorsal mPFC (~25% of the neurons as assessed by Fos-NeuN double-labelling) and weaker Fos induction in the ventral mPFC (~11%). Additionally, systemic injections of the D1-family receptor antagonist SCH23390 (10 µg/kg, s.c.) blocked both yohimbine-induced reinstatement and yohimbine-induced mPFC Fos induction. Furthermore, dorsal, but not ventral, mPFC injections of SCH23390 (0.5, 1.0 µg/side) decreased yohimbine-induced reinstatement of food seeking. Finally, dorsal mPFC SCH23390 injections had no effect on ongoing high-fat pellets self-administration. Our data indicate a critical role of dorsal mPFC dopamine in reinstatement of food seeking induced by the pharmacological stressor yohimbine, and extend previous studies on the role of the dorsal mPFC in stress-induced reinstatement of drug seeking.