Interoceptive “satiety” signals produced by leptin and CCK

The present studies assessed the extent to which the adiposity signal leptin and the brain–gut hormone cholecystokinin (CCK), administered alone or in combination, give rise to interoceptive sensory cues like those that are produced by a low (1 h) level of food deprivation. Rats were trained with cues arising from 1 to 24-h food deprivation as discriminative stimuli. For one group, 24-h food deprivation predicted the delivery of sucrose pellets, whereas 1-h food deprivation did not. Another group received the reversed deprivation level-sucrose contingency. After asymptotic performance was achieved, the effects of leptin and CCK on food intake and on discrimination performance were tested under 24-h food deprivation. In Experiment 1a, leptin administered into the third cerebroventricle (i3vt) at 3.5 or 7.0 μg doses had little effect, compared to saline on food intake or discriminative responding. In Experiment 1b, leptin (7.0 μg, i3vt) combined with CCK-8 (2 μg/kg, i.p.) reduced food intake significantly, but the findings indicated that CCK-8 alone produces interoceptive discriminative cues more like those produced by 1- than 24-h food deprivation. Experiment 2a tested rats with i.p. leptin (0.3 and 0.5 mg/kg). Although neither dose suppressed intake, the 0.3 mg/kg dose produced interoceptive cues like 1-h food deprivation. Experiment 2b tested two doses of CCK-8 (2 and 4 mg/kg, i.p.) and found significant intake suppression and generalization of discrimination with both doses of CCK-8. These findings suggest a role for both leptin and CCK in the production of sensory consequences that correspond to “satiety”.