Overeating after restraint stress in cholecystokinin-a receptor-deficient mice.
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.
Miyasaka
Kyoko
K
Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho Itabashiku, Tokyo, 173-0015 Japan. miyasaka@tmig.or.jp.
Kanai
Setsuko
S
Ohta
Minoru
M
Hosoya
Hiroko
H
Takano
Saeko
S
Sekime
Ayako
A
Sakurai
Chihiro
C
Kaneko
Takao
T
Tahara
Shoichi
S
Funakoshi
Akihiro
A
D000818:Animals; D001835:Body Weight; D002766:Cholecystokinin / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D005744:Gastric Acid; D005746:Gastric Emptying / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D006963:Hyperphagia; D051379:Mice; D043886:Receptor, Cholecystokinin A / Q000235:genetics; D043887:Receptor, Cholecystokinin B / Q000235:genetics; D012844:Sincalide / Q000494:pharmacology
D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D002766:Cholecystokinin; D012844:Sincalide