No relationship between sequence variation in protein coding regions of the Tas1r3 gene and saccharin preference in rats.

Nearly all mammalian species like sweet-tasting foods and drinks, but there are differences in the degree of 'sweet tooth' both between species and among individuals of the same species. Some individual differences can be explained by genetic variability. Polymorphisms in a sweet taste receptor (Tas1r3) account for a large fraction of the differences in consumption of sweet solutions among inbred mouse strains. We wondered whether mice and rats share the same Tas1r3 alleles, and whether this gene might explain the large difference in saccharin preference among rats. We conducted three experiments to test this. We examined DNA sequence differences in the Tas1r3 gene among rats that differed in their consumption of saccharin in two-bottle choice tests. The animals tested were from an outbred strain (Sprague-Dawley; experiment 1), selectively bred to be high- or low-saccharin consumers (HiS and LoS; experiment 2), or from inbred strains with established differences in saccharin preference (FH/Wjd and ACI; experiment 3). Although there was considerable variation in saccharin preference among the rats there was no variation in the protein-coding regions of the Tas1r3 gene. DNA variants in intronic regions were detected in 1 (of 12) outbred rat with lower-than-average saccharin preference and in the ACI inbred strain, which also has a lower saccharin preference than the FH/Wjd inbred partner strain. Possible effects of these intronic nucleotide variants on Tas1r3 gene expression or the presence of T1R3 protein in taste papillae were evaluated in the ACI and FH/Wjd strains. Based upon the results of these studies, we conclude that polymorphisms in the protein-coding regions of the sweet receptor gene Tas1r3 are uncommon and do not account for individual differences in saccharin preference for these strains of rats. DNA variants in intron 4 and 5 are more common but appear to be innocuous.

Ingestional responses to metabolic challenges in rats selectively bred for high and low saccharin intake.

Rats selectively bred on the basis of saccharin intake also differ on some measures of emotional reactivity. The present studies were designed to contribute to our understanding of this association. Rats selectively bred for relatively high (HiS) versus low (LoS) saccharin intake were tested in two paradigms useful in assessing the ability to respond adaptively to internal perturbations of metabolic regulation or to external events that may produce metabolic challenges. The first study concerned slow-onset (regular insulin) and rapid-onset (2-deoxy-D-glucose [2-DG], fast-acting insulin) glucoprivation and resultant feeding behavior. LoS and HiS lines did not differ in response to saline or slow-onset challenges, but LoS rats ate less in the first half hour after rapid-onset challenges; the line differences were eliminated by pretreatment with caffeine. The second study revealed significantly higher plasma corticosterone (CORT) among LoS rats relative to HiS rats, both in the light and in the dark. Preliminary assessments after a single stressor and a single dose of dexamethasone showed, respectively, CORT elevation and suppression that was comparable in the two lines. These results add further support to the ideas that voluntary consumption of saccharin is related to the expression of classically defined emotional behaviors, and that responsiveness to diverse metabolic challenges may share a common basis, such as genetic pleiotropism.