Western diet and the weakening of the interoceptive stimulus control of appetitive behavior

• Rats learn to use deprivation states as discriminative cues for sucrose.
• When trained in compound, food cues do not overshadow energy state cues for appetitive control.
• Western diet intake impairs the ability to use food deprivation cues.
• Hippocampal lesions reduce sensitivity to the interoceptive satiety cue CCK.

In obesogenic environments food-related external cues are thought to overwhelm internal cues that normally regulate energy intake. We investigated how this shift from external to internal stimulus control might occur. Experiment 1 showed that rats could use stimuli arising from 0 and 4 h food deprivation to predict sucrose delivery. Experiment 2 then examined (a) the ability of these deprivation cues to compete with external cues and (b) how consuming a Western-style diet (WD) affects that competition. Rats were trained to use both their deprivation cues and external cues as compound discriminative stimuli. Half of the rats were then placed on WD while the others remained on chow, and external cues were removed to assess learning about deprivation state cues. When tested with external cues removed, chow-fed rats continued to discriminate using only deprivation cues, while WD-fed rats did not. The WD-fed group performed similarly to control groups trained with a noncontingent relationship between deprivation cues and sucrose reinforcement. Previous studies provided evidence that discrimination based on interoceptive deprivation cues depends on the hippocampus and that WD intake could interfere with hippocampal functioning. A third experiment assessed the effects of neurotoxic hippocampal lesions on weight gain and on sensitivity to the appetite-suppressing effects of the satiety hormone cholecystokinin (CCK). Relative to controls, hippocampal-lesioned rats gained more weight and showed reduced sensitivity to a 1.0 ug but not 2.0 or 4.0 ug CCK doses. These findings suggest that WD intake reduces utilization of interoceptive energy state signals to regulate appetitive behavior via a mechanism that involves the hippocampus.