Palatable food avoidance and acceptance learning with different stressors in female rats

Stress activates the hypothalamus–pituitary–adrenal (HPA) axis leading to the release of glucocorticoids (GC). Increased activity of the HPA axis and GC exposure has been suggested to facilitate the development of obesity and metabolic syndrome. Nonetheless, different stressors can produce distinct effects on food intake and may support different directions of food learning e.g. avoidance or acceptance. This study examined whether interoceptive (LiCl and exendin-4) and restraint stress (RS) support similar or distinct food learning. Female rats were exposed to different stressors after their consumption of a palatable food (butter icing). After four palatable food–stress pairings, distinct intakes of the butter icing were observed in rats treated with different stressors. Rats that received butter icing followed by intraperitoneal injections of LiCl (42.3 mg/kg) and exendin-4 (10 μg/kg) completely avoided the palatable food with subsequent presentations. In contrast, rats experiencing RS paired with the palatable food increased their consumption of butter icing across trials and did so to a greater degree than rats receiving saline injections. These data indicate that interoceptive and psychosocial stressors support conditioned food avoidance and acceptance, respectively. Examination of c-Fos immunoreactivity revealed distinct neural activation by interoceptive and psychosocial stressors that could provide the neural basis underlying opposite direction of food acceptance learning.

► Restraint stress as an unconditioned stimulus facilitates overconsumption of a palatable food.
► Interoceptive stressors such as LiCl and exendin-4 support conditioned food avoidance learning.
► Rats are less adaptive to stress induced by LiCl or exendin-4 than by restraint.
► A psychogenic restraint stress may play a role in the development of binge eating disorders.