Abstract
BackgroundEating 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.ResultsWhile 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.ConclusionsThese 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.
Highlights
Our findings demonstrate that while Control animals showed a profound conditioned suppression of chocolate seeking during presentation of conditioned stimulus, previously food deprived (FD) animals revealed a clearcut preference for the chamber containing chocolate, indicating that previous exposure to a food restriction experience induces food seeking/intake despite its possible harmful consequences, which is an index of compulsive behavior
Experiment 1: Conditioned Suppression Test in Control and Food Deprived groups Control and Food Deprived mice showed no significant difference in total time spent in chocolate-chamber (CC) in comparison with empty-safe chamber (E-SC) during the training phase and on the choice check test day
Results from chocolate intake during conditioned suppression test day show thatprevious exposure to a stressful food restriction experience induces food seeking/ intake despite its possible harmful consequences (Figure 1B2), which is an index of compulsive behavior
Summary
Chronic stressful experiences and caloric restriction are the most powerful triggers of eating disorders in human and animals. 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, modeling food seeking in spite of harmful consequences in mice. No evidence has been reported of continued food seeking/intake despite its possible harmful consequences, an index of compulsive behavior [21]. Using a new conditioned suppression paradigm, we investigated whether the ability of a foot-shock-paired conditioned stimulus (CS) to suppress chocolate-seeking behavior was reversed by exposure to chronic stress, modeling food seeking in spite of harmful consequences in mice. Chocolate is the most commonly craved food and chocolate craving and addiction have been proposed in humans [25]
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