Food seeking in spite of harmful consequences is under prefrontal cortical noradrenergic control.
BACKGROUND
Eating disorders are multifactorial psychiatric disorders. Chronic stressful experiences and caloric restriction are the most powerful triggers of eating disorders in human and animals. Although compulsive behavior is considered to characterize pathological excessive food intake, to our knowledge, no evidence has been reported of continued food seeking/intake despite its possible harmful consequences, an index of compulsive behavior. Brain monoamine transmission is considered to have a key role in vulnerability to eating disorders, and norepinephrine in medial prefrontal cortex has been shown to be critical for food-related motivated behavior.Here, using a new paradigm of conditioned suppression, we investigated whether the ability of a foot-shock-paired conditioned stimulus to suppress chocolate-seeking behavior was reversed by previous exposure to a food restriction experience, thus modeling food seeking in spite of harmful consequences in mice. Moreover, we assessed the effects of selective norepinephrine inactivation in medial prefrontal cortex on conditioned suppression test in stressed and caloric restricted mice.


RESULTS
While Control (non food deprived) animals showed a profound conditioned suppression of chocolate seeking during presentation of conditioned stimulus, previously food restricted animals showed food seeking/intake despite its possible harmful consequences. Moreover, food seeking in spite of harmful consequences was prevented by selective norepinephrine inactivation, thus showing that prefrontal cortical norepinephrine is critical also for maladaptive food-related behavior.


CONCLUSIONS
These findings indicate that adaptive food seeking/intake can be transformed into maladaptive behaviors and point to "top-down" influence on eating disturbances and to new targets for therapy of aberrant eating behaviors.
Santa Lucia Foundation, European Centre for Brain Research (CERC), via del Fosso di Fiorano 64, Rome 00143 Italy.
Emanuele Claudio
EC
Latagliata
Enrico
E
Patrono
Stefano
S
Puglisi-Allegra
Rossella
R
Ventura
D000818:Animals; D001362:Avoidance Learning; D001835:Body Weight; D002099:Cacao; D003214:Conditioning, Classical; D004195:Disease Models, Animal; D004597:Electroshock; D005215:Fasting / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D001068:Feeding and Eating Disorders; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009483:Neuropsychological Tests; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011897:Random Allocation; D013315:Stress, Psychological / Q000503:physiopathology*; D013997:Time Factors
D009638:Norepinephrine