Role of dopamine in dorsal medial prefrontal cortex in yohimbine-induced reinstatement of food seeking in rats

In humans, relapse to maladaptive eating habits during dieting is often provoked by stress.Weadapted a drug relapse-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, an alpha-2 adrenoceptor antagonist, that causes stress-like responses in humans and laboratory animals, reliably reinstates food seeking.Werecently found that yohimbine-induced reinstatement of food seeking is attenuated by systemic injections of SCH23390 (a D1-family receptor antagonist) but not clonidine (an alpha-2 adrenoceptor agonist). 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 10–14 days by removing the pellets. Subsequently, we tested the effect of systemic injections of yohimbine (0, 2 mg/kg) on reinstatement of food seeking. In Exp. 1we found that yohimbine-induced reinstatement was associated with strong induction of Fos (a marker of neuronal activity) in the dorsal mPFC and weaker Fos induction in the ventral mPFC. In Exp. 2 we found that dorsal but not ventral mPFC injections of the D1-family receptor antagonist SCH23390 (0.5, 1.0g/side) decreased yohimbine-induced reinstatement of food seeking. Our data indicate a critical role of dorsal mPFC dopamine in reinstatement food seeking induced by the pharmacological stressor yohimbine.