In mammals, including humans, a brain-gut hormone, cholecystokinin (CCK) mediates the satiety effect via CCK-A receptor (R). We generated CCK-AR gene-deficient (−/−) mice and found that the daily food intake, energy expenditure, and gastric emptying of a liquid meal did not change compared with those of wild-type mice. Because CCK-AR(−/−) mice show anxiolytic status, we examined the effects of restraint stress. Seven hours of restraint stress was found to significantly decrease both body weight and food intake during the subsequent 3 days in all tested animals. On the fourth day after restraint stress, the CCK-AR(−/−) mice showed a significantly higher level of daily food intake than prior to stress, and food intake recovered to prestress levels in the wild-type mice. Since peripheral CCK-AR has been known to mediate gastric emptying, both gastric emptying and gastric acid secretion were determined to examine the mechanism of overeating in CCK-AR(−/−) mice. Neither gastric emptying nor gastric acid secretion differed between CCK-AR(−/−) and wild-type mice on the fourth day after stress. In contrast, however, the contents of dopamine and its metabolites in the cerebral cortex of CCK-AR(-/-) mice were increased by stress, but were rather decreased in wild-type mice. Changes in 5-hydroxytryptamine (5-HT) and its metabolite 5HIAA did not differ between the genotypes. In conclusion, CCK-AR(−/−) mice showed overeating after restraint stress, and dopaminergic hyperfunction in the brain of these mice was observed. The present evidence suggests that the CCK-AR function, possibly via altering the dopaminergic function, might be involved in overeating after stress.