Stress- and pellet-priming-induced reinstatement of food seeking and neuronal activation in c-fos-GFP transgenic female rats: Role of ovarian hormones.

Relapse to maladaptive eating habits during dieting is often provoked by stress. Women may be particularly vulnerable to stress-induced relapse due to fluctuations in ovarian hormones. We used ovariectomized (OVX) or sham OVX c-fos-GFP (green fluorescent protein) transgenic female rats, which express GFP in strongly activated neurons, to study brain areas involved in stress- and pellet-priming-induced reinstatement as well as the potential role of ovarian hormones in reinstatement and neuronal activation. Food-restricted OVX or sham rats were trained for 3 h per day to lever press for delivery of palatable food pellets, paired with a discrete tone-light cue. Pellet intake was then assessed after systemic injections of the pharmacological stressor yohimbine (0, 0.5, 1.0, and 2 mg/kg, i.p.). Subsequently, lever pressing was extinguished over 20 sessions and reinstatement of food seeking was assessed after yohimbine injections or pellet priming (0, 1, 2, and 4 non-contingent pellets, delivered at session onset). Compared to sham rats, OVX rats showed a modest decrease in pellet-priming-induced reinstatement, but not in pellet intake, yohimbine-induced increases in pellet intake, or yohimbine-induced reinstatement. In both OVX and sham rats, yohimbine- and pellet-priming induced reinstatement was associated with increased GFP expression in dorsal and ventral mPFC. We conclude that ovarian hormones play a role in relapse to food seeking induced by acute re-exposure to food taste and smell but not in stress-induced feeding or relapse in our rat model.