Normal feeding and body weight in Fischer 344 rats lacking the cholecystokinin-1 receptor gene.

Abstract

A large body of evidence has demonstrated that one mechanism by which cholecystokinin (CCK) inhibits food intake through activation of CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. OLETF rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic, obese, and predisposed to type 2 diabetes. Recently, by introgressing the OLETF-derived, CCK1R-null gene onto a Fischer 344 genetic background, we have been able to generate a CCK1R-deficient, congenic rat strain, F344.Cck1r(-/-), that in contrast to OLETF rats, possesses a lean and normoglycemic phenotype. In the present study, the behavioral and neurobiological phenotype of this rat strain was characterized more fully. As expected, intraperitoneal injections of CCK-8 inhibited intake of chow and Ensure Plus and induced Fos responses in the area postrema and the gelatinosus, commissural and medial subdivisions of the nucleus tractus solitarius of wild-type F344.Cck1r(+/+) rats, whereas CCK-8 was without effect on food intake or Fos induction in the F344.Cck1r(-/-) rats. F344.Cck1r(-/-) and F344.Cck1r(+/+) rats did not differ in body weight and showed comparable weight gain when maintained on Ensure Plus for 2 weeks. Also, no difference was found in 24-h food intake, and dark-phase meal frequency or meal size between F344.Cck1r(+/+) and F344.Cck1r(-/-) rats. As expected, blockade of endogenous CCK action at CCK1R increased food intake and blocked the effects of peripheral CCK-8 in wild-type F344.Cck1r(+/+) rats. These results confirm that in rats with a F344 background, CCK-1R mediates CCK-8-induced inhibition of food intake and Fos activation in the hindbrain and demonstrate that selective genetic ablation of CCK1R is not associated with altered meal patterns, hyperphagia, or excessive weight gain on a palatable diet.

• Authors: J E Blevins, J Overduin, J M Fuller, D E Cummings, K Matsumoto, D H Moralejo
• Journal: Brain research (Brain Res) Vol. 1255 Pg. 98-112 (Feb 19 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19111529 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Peptide Fragments
• Proto-Oncogene Proteins c-fos
• Receptor, Cholecystokinin A
• cholecystokinin 8
• Cholecystokinin

Topics

• Animals
• Body Weight (physiology)
• Cholecystokinin (administration & dosage, pharmacology)
• Eating (physiology)
• Feeding Behavior (physiology)
• Genotype
• Immunohistochemistry
• Injections, Intraperitoneal
• Male
• Peptide Fragments (administration & dosage, pharmacology)
• Polymerase Chain Reaction
• Proto-Oncogene Proteins c-fos (metabolism)
• Rats
• Rats, Inbred F344
• Rats, Transgenic
• Receptor, Cholecystokinin A (deficiency, genetics, metabolism)