The contribution of taste bud populations to bitter avoidance in mouse strains differentially sensitive to sucrose octa-acetate and quinine

Mice of the SWR/J (SW) strain avoid orally delivered sucrose octa-acetate (SOA), whereas the mice of the C3HeB/FeJ (C3) strain are insensitive to SOA. Mice of both strains and of a congenic strain (C3.SW) that shares more than 99% of the C3 genome, were tested in a taste-salient brief-access taste test for responses to SOA and quinine hydrochloride, before and after transection of the glossopharyngeal or chorda tympani nerve, or sham surgery. Prior to surgery, congenic SOA tasters (C3.SW(T)) were phenotypically identical to the SW strain in avoidance of SOA, but showed a greater reduction in sensitivity after nerve transection. For quinine avoidance, which is thought to be a polygenic trait, SW mice showed the greatest sensitivity to quinine, C3 the least and C3.SW(T) mice were different from both parental strains, showing intermediate sensitivity. Nerve transections had only a moderate effect on quinine sensitivity, suggesting that both anterior and posterior taste bud fields contribute to behavioral quinine avoidance. These findings are discussed with regard to the distribution in the oral cavity of putative taste receptors for quinine and SOA and the peripheral organization of bitter taste.     

Taste sensitivities to PROP and PTC vary independently in mice

Mammals use common mechanisms to detect, transduce and process taste stimulus information. For example, they share families of receptors that respond to amino acids, and sweet- and bitter-tasting stimuli. Nonetheless, it also clear that different species exhibit unique taste sensitivities that may reflect specific genetic variations. In humans, sensitivities to the chemically similar, bitter-tasting compounds 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC) are heritable and strongly correlated, suggesting a common genetic basis. However, it is unknown whether PROP and PTC taste sensitivities are similarly correlated in mice. Here we report that PROP and PTC taste sensitivities vary independently between two inbred strains of mice. In brief-access taste tests C3HeB/FeJ (C3) and SWR/J (SW) mice possess similar taste sensitivity to PTC, while SW mice are significantly more sensitive to PROP than are C3 mice. In two-bottle preference tests, however, SW mice display greater aversion to both compounds. This discrepancy may be explained by the observation that SW mice consumed taste solutions at a greater rate during the intake test than did C3 mice. Therefore, PTC avoidance is correlated with the amount of PTC consumed in the intake tests rather than the concentration of PTC tested. These findings suggest that post-ingestive factors play a significant role in PTC avoidance during intake tests and highlight an important advantage of brief-access tests over intake tests in resolving the gustatory and post-ingestive contributions to taste-related behaviors. Most strikingly, these results demonstrate that in mice, unlike in humans, PTC and PROP taste sensitivities vary independently, thereby suggesting a subtle functional diversity of bitter-taste mechanisms across mammalian species.     

The relationship between PROP and ethanol preferences: an evaluation of 4 inbred mouse strains

Ethanol's taste attributes undoubtedly contribute to the development of drug preference. Ethanol's taste is both sweet and bitter. Taster status for bitter 6-n-propylthiouracil (PROP) has been proposed as a genetic marker for alcoholism; however, human results are conflicting. We collected preference scores for both tastants in 4 mouse strains selected on the basis of previously reported taste preference, with the generally accepted idea that inbred mice show minimal within-strain variation. Eighty-eight male mice (22 per strain) participated. The strains were as follows: C57BL/6J, ethanol preferring; BALB/cJ, ethanol avoiding; SWR/J, PROP avoiding; and C3HeB/FeJ, PROP neutral. Using a brief-access (1-min trials) 2-bottle preference test, we assessed the taste response of each strain to PROP and ethanol on separate days. Although PROP avoiding versus neutral mice could be segregated into significantly different populations, this was not the case for ethanol avoiding versus preferring mice, and all strains showed high variability. On average, only BALB/cJ, SWR/J, and C3HeB/FeJ mice conformed to their literature-reported preferences; nonetheless, there were a substantial number of discordant animals. C57BL/6J did not conform to previous results, indicating that they are ethanol preferring. Finally, we did not observe a significant relationship between PROP and ethanol preferences across strains. The high variability per strain and the number of animals in disagreement with their respective literature-reported preference raise concerns regarding their utility for investigations underlying mechanisms of taste-mediated ingestive responses. Absent postingestive consequences, the brief-access results suggest a possible degree of previously masked polymorphisms in taste preferences or a more recent drift in underlying genetic factors. The absence of a relationship between PROP and ethanol indicates that the bitter quality in ethanol may be more highly related to other bitter compounds that are mediated by different genetic influences.     

The relative affective potency of glycine, L-serine and sucrose as assessed by a brief-access taste test in inbred strains of mice

In general, rodents prefer both sucrose and L-serine relative to water and treat both compounds as possessing a similar taste quality (e.g. 'sweetness') despite that they are believed to bind with different T1R heterodimeric receptors in taste bud cells. We assessed the affective potency of these compounds along with glycine, which is thought to bind with both T1R receptor complexes, using a brief-access taste test in a gustometer. Unconditioned licking responses of two 'taster' strains (C57BL/6J and SWR/J), which display high preference for low concentrations of sucrose, and two 'non-taster' (129P3/J and DBA/2J) strains, which display blunted preference for low concentrations of sucrose, were measured during 5 s trials of varying concentrations of a single compound when mice (n=10/strain/stimulus) were non-deprived and when access to home-cage water was restricted. In non-deprived mice, sucrose generated monotonically increasing concentration-response curves regardless of strain, whereas glycine was only marginally effective at stimulating licking and L-serine produced relatively flat functions. The profile of responsiveness across strains was more complex than expected. For example, when tested with sucrose in the non-deprived condition, the 129P3/J non-taster strain surpassed the responsiveness of taster mice at mid-range to high concentrations. Under water-restricted conditions, these mice also were significantly more responsive to high concentrations of both sucrose and glycine compared with the other strains when stimulus licking was standardized relative to water. Thus, the affective potency of the stimuli tested here seems to be related to the ability of the compounds to bind with the T1R2+3 receptor complex. However, the profile of strain responsiveness to these tastants in the brief-access test does not appear to be simply explained by the sweetener 'taster' status of the strain.     

SW.B6-Soab Nontaster Congenic Strains Completed and a Sucrose Octaacetate Congenic Quartet Tested with other Bitters

Ten SW.B6 SOA nontaster strains congenic with the SWR/J SOAtaster inbred strain were bred via repeated backcross-intercrosscycles, with selection for nontasting in each cycle. Preferenceratio distributions and phenotypic proportions across cyclesat 0.1 mM SOA were consistent with monogenic predictions. TheSW.B6 mice completed a congenic quartet with the SWR/J, B6.SWSOA taster and C57BL/6J SOA nontaster strains. The Soa locuscontrolled avoidance differences within the quartet for SOA,raffinose undecaacetate, glucose pentaacetate and brucine. Backgroundgenes not linked to Soa controlled avoidance differences forL-phenylalanine and ethanol. Avoidance of bitter picric acidwas influenced by the Soa locus, but avoidance of acetic acidwas not. The quartet pattern for quinine HCl was unclear, withindications of both Soa and background effects. Two forms ofribose tetraacetate yielded different patterns. Avoidance differencescontrolled by the Soa locus were found for the pyranose form;however, all four strains avoided the furanose form. The pleiotropiceffects of Soa allele substitution within the quartet were limitedto a subset of bitter compounds. Chem. Senses 21: 507–517,1996.     

Variation in nicotine consumption in inbred mice is not linked to orosensory ability

Genetic studies of nicotine addiction in mice have utilizedthe oral self-administration model. However, it is unclear ifstrain differences in nicotine consumption are influenced byvariation in bitter taste sensitivity. We measured both nicotineconsumption and nicotine brief-access licking behavior in severalcommonly used inbred strains of mice that were previously shownto differ in nicotine consumption. A/J (A), C57BL/6J (B6), andDBA/2J (D2) mice were given a 2-bottle choice test with a singleconcentration of nicotine (75 µg/ml; nicotine vs. water).Mice of these strains were also tested with a range of nicotineconcentrations (5–400 µg/ml) using a brief-accesstest, which measures orosensory response and minimizes postingestiveeffects. Although B6 mice consumed more 75-µg/ml nicotinethan A or D2 mice in the 2-bottle test, these strains did notdiffer in level of aversion to nicotine when tested with thebrief-access procedure. Strain differences in orosensory responseto nicotine were not found; yet, differences emerged duringthe 2-bottle tests. This study provides evidence that variationin intake level of nicotine is likely not due to differencesin taste or trigeminal sensitivity but likely due to postingestivefactors.     

Intermediate sucrose octa-acetate sensitivity suggests a third allele at mouse bitter taste locus Soa and Soa-Rua identity

Mice have been characterized as either tasters or non-tastersof the bitter compound sucrose octa-acetate(SOA). However, 11of 17 supposedly non-taster inbred strains were found to avoid1 mM SOA. All 17 strains were indifferent to 0.1 mM SOA. Tasterstrains avoided both concentrations. The intermediate phenotypewas dubbed demitaster. A consistent phenotypic dominance orderwas found in crosses among both inbred and outbred strains (taster> non-taster > demitaster). Demitasters were found (withtasters) in an outbred strain showing monogenic segregationfor SOA avoidance. This, plus monogenic segregation in a back-crossof taster to demitaster inbred strains, suggested a third alleleat the Soa locus (Soa^c). Demitaster allelism was supported bythe strong associations found in 15 strains between the threeSOA phenotypes and HindIII restriction fragment patterns forthe closely linked Prp (proline rich protein) loci. SOA demitasterstrains were also intermediate in raffinose undeca-acetate (RUA)avoidance. Furthermore, B6.SW-Soa² congenic mice avoided notonly SOA, but RUA and eight other acetylated sugars. A previouslyproposed separate RUA-sensitivity gene (Rua) thus appeared tobe redundant.     

Polygenic determination of quinine aversion among mice

There are substantial differences among inbred mouse strainsin avoidance of quinine solutions in two-bottle preference tests.x A Mendelian cross-breeding experiment was conducted to testthe hypothesis that a single locus Qui has a major influenceon quinine aversion. Inbred strains C57B1/6J (B6, avoider) andC3HeB/FeJ (C3, indifferent) were progenitors of two segregatinggenerations. Phenotypic ratios for 100 µM and 30 µMquinine sulfate (QSO4) in these generations were not consistentwith ratios expected for a single gene. Frequency distributionsfor individual preference ratios were more characteristic ofa polygenic trait. An outbred strain (CFW/Crl) which displayssegregation for the Soa locus was tested for both QSO4 and sucroseocta-acetate (SOA) avoidance. Correlated avoidance patternsfor the two bitter compounds were found in these mice. A Soaeffect might not have been seen in the C3.B6 cross because bothstrains are relatively poor SOA avoiders. A second Mendeliancross was made between strains C3 and SWR/J (SW, SOA and QSO4avoider). One segregating generation was tested with both compounds.In these mice, as in the CFW population, QSO4 aversion was correlatedwith SOA aversion. These results suggest that quinine aversionis polygenic, that there is a relationship between SOA sensitivityand quinine sensitivity, and that this association may be theresult of variation at the Soa locus.     

Mice bearing Acads mutation display altered postingestive but not 5-s orosensory response to dietary fat

A previous survey of mouse inbred strains revealed a wide range in self-selected fat intake, from 26 to 83% of energy. The BALB/cByJ strain selected a lower percentage of fat intake (36%) than all other strains tested except for the CAST/Ei. BALB/cByJ mice are deficient in the short-chain acyl-CoA dehydrogenase (SCAD) enzyme due to a spontaneous mutation in Acads. We hypothesized that this deficiency would alter fat appetite and used three behavioral test paradigms to compare the response of BALB/cByKz. Acads -/- and BALB/cByKz. Acads +/+ mice to fat stimuli. First, during 10-day exposure to a macronutrient self-selection diet, Acads -/- mice consumed proportionately less fat and more carbohydrate than Acads +/+ mice, yet total energy intake was similar between strains. Next, in 48-h two-bottle preference tests, Acads +/+ mice displayed a preference for 50% corn oil, but Acads -/- mice did not. Finally, in brief-access taste tests employing successive 5-s presentations of corn oil in an ascending concentration series ending with 50%, there were no effects of strain on total licks, indicating that Acads does not alter acute orosensory response to this fat stimulus. With 15-s presentations, however, the Acads +/+ mice licked more of the 50% oil than Acads -/-, suggesting orosensory effects related to the increased exposure time. In contrast to corn oil, there were no strain differences in licking response to sucrose solution in either the two-bottle or brief-access taste tests. The observation that SCAD-deficient mice display altered postingestive responses to dietary fat provides further evidence for the metabolic control of feeding.     

A common polygenic basis for quinine and PROP avoidance in mice

Inbred strains of mice (Mus musculus) differ greatly in ability to taste various bitter compounds. For some compounds, the differences result from allelic variation at a single locus. However, segregation patterns incompatible with monogenic inheritance have been found for quinine avoidance. The Soa bitter sensitivity locus exerts some influence on this phenotype, but an unknown number of other loci also contribute. Relative avoidance patterns for quinine sulfate in panels of naive inbred strains resembled avoidance patterns for 6-n-propyl-2- thiouracil (PROP), suggesting a common genetic basis. In particular, C57BL/6J mice strongly avoided both 0.1 mM quinine sulfate and 1 mM PROP in two-bottle preference tests, whereas C3H/HeJ mice were indifferent to both. Therefore, 12 BXH/Ty recombinant inbred strains, derived from these strains, were tested with both solutions to begin identification of the unknown bitter loci. Naive mice were tested for four consecutive days with each compound (order counterbalanced). Some BXH/Ty strain means resembled those of the parent strains, but others were intermediate. This indicated recombination among loci affecting avoidance, and therefore polygenic inheritance. The strain means were highly correlated across compounds (r = 0.98), suggesting that the same polygenes controlled both phenotypes. The BXH/Ty means for both compounds were then compared with the strain genotypes at 212 chromosome position markers distributed throughout the genome. Eight markers on five chromosomes (3, 6, 7, 8 and 9) yielded significant correlations. Six of the markers were correlated with both phenotypes, again suggesting common polygenic inheritance. The marker with the highest correlation was Prp, tightly linked to Soa on chromosome 6. The correlated marker regions likely contain quantitative trait loci affecting bitter avoidance. The phenotypic similarity of PROP to quinine, rather than to phenylthiourea, apparently stemming from a common polygenic basis, indicates a difference between mice and humans in gustatory organization related to bitters.      

Strain differences among mice in taste psychophysics of sucrose octaacetate

SWR/J inbred mice consistently avoided a 10^–4 M sucroseoctaacetate (SOA) solution in unconditioned two-bottle preferencetests whereas mice of all other inbred strains tested did not(confirming a previous report that used SWR mice of a differentsubline). In a conditioned taste aversion procedure SWR/J miceavoided SOA at concentrations from 10^–3 M to 10^–7M but not at 10^–8 M. Various other inbred strains firstfailed to avoid SOA at concentrations from 10^–3 M to 10^–5M. The major strain difference between SWR and other inbredmice was robust across rearing regimes and when tested withother psychophysical procedures. In single-bottle, free-lickingtests SWR/J mice differed from C57L/J mice in response to SOAfollowing extremely brief exposure to the SOA.The SOA detectionthreshold differences indicated by these psychophysical proceduresare also consistent with differences reported from electrophysiologicalrecordings from glossopharyngeal and chorda tympani nerves inmice of several of the same strains.     

Preference for sucralose predicts behavioral responses to sweet and bittersweet tastants

Rats can be classified as either sucralose avoiders (SA) or sucralose preferrers (SP) based on their behavioral responses in 2-bottle preference, 1-bottle intake, and brief-access licking tests. The present study demonstrates that this robust phenotypic variation in the preference for sucralose predicts acceptance of saccharin, an artificial sweetener with a purported concentration-dependent "bitter" side taste and a 0.25 M sucrose solution adulterated with increasing concentrations of quinine hydrochloride (QHCl). Specifically, SA displayed decreased preference for and intakes of saccharin (≥41.5 mM) and sucrose-QHCl (>0.5 mM QHCl) solutions, relative to SP. In a second experiment involving brief-access (30-s) tests, SP and SA did not differ in their unconditioned licking responses across a range of sodium chloride or QHCl solutions (0.03-1 mM). However, the acceptability threshold for sucrose was lower in SA, relative to SP (0.06 and 0.13 M, respectively). Our findings suggest that phenotypic differences in sucralose preference are indicative of a more general difference in the hedonic processing of stimuli containing "bittersweet" or "sweet" taste qualities.     

High-resolution genetic mapping of the sucrose octaacetate taste aversion (Soa) locus on mouse Chromosome 6

An acetylated sugar, sucrose octaacetate (SOA), tastes bitter to humans and has an aversive taste to at least some mice and other animals. In mice, taste aversion to SOA depends on allelic variation of a single locus, Soa. Three Soa alleles determine `taster' (Soa <sup>a</sup> ), `nontaster' (Soa ^b ), and `demitaster' (Soa ^c ) phenotypes of taste sensitivity to SOA. Although Soa has been mapped to distal Chromosome (Chr) 6, the limits of the Soa region have not been defined. In this study, mice from congenic strains SW.B6-Soa ^b , B6.SW-Soa ^a , and C3.SW-Soa ^a/c and from an outbred CFW strain were genotyped with polymorphic markers on Chr 6. In the congenic strains, the limits of introgressed donor fragments were determined. In the outbred mice, linkage disequilibrium and haplotype analyses were conducted. Positions of the markers were further resolved by using radiation hybrid mapping. The results show that the Soa locus is contained in a ∼1-cM (3.3–4.9 Mb) region including the Prp locus. Received: 5 February, 2001 / Accepted: 1 May, 2001     

PLCbeta2-independent behavioral avoidance of prototypical bitter-tasting ligands

Using a brief-access taste assay, we show in the present report that although phospholipase C beta2 knockout (PLCbeta2 KO) mice are unresponsive to low- and midrange concentrations of quinine and denatonium, they do significantly avoid licking higher concentrations of these aversive compounds. PLCbeta2 KO mice displayed no concentration-dependent licking of the prototypical sweetener sucrose but were similar to wild-type mice in their responses to citric acid and NaCl, notwithstanding some interesting exceptions. Although these findings confirm an essential role for PLCbeta2 in taste responsiveness to sucrose and to low- to midrange concentrations of quinine and denatonium in mice as previously reported, they importantly suggest that higher concentrations of the latter two compounds, which are bitter to humans, can engage a PLCbeta2-independent taste transduction pathway.     

Taste solution preferences of C57BL/6J and 129X1/SvJ mice: influence of age, sex, and diet

To examine whether age influences taste solution preferences, we measured taste preferences of C57BL/6J and 129X1/SvJ mice given a series of 48-h 2-bottle tests with a choice between water and one of the following taste solutions: 2 mM saccharin, 5 mM citric acid, 30 microM quinine hydrochloride, 75 mM sodium chloride (NaCl), 10 mM inosine monophosphate (IMP), 50 mM calcium chloride (CaCl(2)), and 10% ethanol. We tested separate groups of male mice fed Teklad 8604 chow at ages 4, 6, 9, 12, 15, 20, 25, 30, 40, and 50 weeks and retested some of these mice at 54, 75, and 100 weeks and again at 125 weeks. Female mice fed chow were tested at ages 4, 12, 25, and 50 weeks and retested at 54, 75, 100, and 125 weeks. Male mice fed AIN-93G semisynthetic diet were tested at ages 4, 12, 25, and 50 weeks and retested at 54, 75, and 100 weeks. Concentration-response functions for each taste solution were collected from male and female mice fed chow aged 8 or 125 weeks. In general, the results showed that age had little effect on taste preferences. Exceptions included 1) a small increase in quinine hydrochloride preference between 54 and 125 weeks in mice of both strains and sexes, 2) a marked increase in NaCl preference between 4 and 12 weeks in female B6 mice, 3) a gradual decrease in IMP preference between 4 and 125 weeks in male and female 129 mice, 4) a marked decrease in CaCl(2) preference between 54 and 125 weeks in male and female 129 mice, and 5) a marked reduction in ethanol preference between 4 and 12 weeks in male B6 mice fed AIN-93G diet but not chow. These results show that over a wide range and with the exceptions noted, age contributes little to the variation in taste preferences observed in C57BL/6J and 129X1/SvJ mice.     

Contribution of alpha-gustducin to taste-guided licking responses of mice

We examined the necessity of alpha-gustducin, a G protein alpha-subunit expressed in taste cells, to taste-mediated licking responses of mice to sapid stimuli. To this end, we measured licking responses of alpha-gustducin knock-out (Gus-/-) mice and heterozygotic littermate controls (Gus+/-) to a variety of 'bitter', 'umami', 'sweet', 'salty' and 'sour' taste stimuli. All previous studies of how Gus-/- mice ingest taste stimuli have used long-term (i.e. 48 h) preference tests, which may be confounded by post-ingestive and/or experiential effects of the taste stimuli. We minimized these confounds by using a brief-access taste test, which quantifies immediate lick responses to extremely small volumes of sapid solutions. We found that deleting alpha-gustducin (i) dramatically reduced the aversiveness of a diverse range of 'bitter' taste stimuli; (ii) moderately decreased appetitive licking to low and intermediate concentrations of an 'umami' taste stimulus (monosodium glutamate in the presence of 100 microM amiloride), but virtually eliminated the normal aversion to high concentrations of the same taste stimulus; (iii) slightly decreased appetitive licking to 'sweet' taste stimuli; and (iv) modestly reduced the aversiveness of high, but not low or intermediate, concentrations of NaCl. There was no significant effect of deleting alpha-gustducin on licking responses to NH4Cl or HCl.     

Hydrolysis of sucrose octa-acetate: qualitative differences in taster and demistaster avoidance phenotypes

Calcium hydroxide and sodium hydroxide were used to hydrolysesucrose octa-acetate (SOA) as a means of evaluating the taster(Soa^a) and demitaster (Soa^c) allelic phenotypes of the geneticlocus Soa. The SWR/J (taster) inbred strain and the B6.SW Soa^a(taster) congenic strain were demonstrated to cease avoidingupon nearly complete hydrolysis of 10^–5 M SOA with calciumhydroxide Or sodium hydroxide and of 10^–4 M SOA with calciumhydroxide. The BALB/cByJ, C3HeB/FeJ and DBA/2J (demitaster)inbred strains were demonstrated to cease avoiding after onlya partial hydrolysis of 10^–3 M SOA using calcium hydroxide.It is suggested that specificity for the number or placementof the acetates of SOA underlies the difference between thetaster and demitaster phenotypes.     

Amiloride is an ineffective conditioned stimulus in taste aversion learning in C57BL/6J and DBA/2J mice

The epithelial sodium channel (ENaC) blocker amiloride has been shown to increase the behaviorally measured NaCl detection threshold in mice. In this study, a conditioned taste aversion (CTA) paradigm was used to examine whether 100 microM amiloride has a perceptible taste that could contribute to this observed decrease in behavioral responsiveness. Eighty-four C57BL/6J (B6) and 64 DBA/2J (D2) mice were divided into eight groups (n=8-12 per group), in which half received an injection of 0.15 M LiCl (2 mEq/kg) and the other half an equivalent saline injection, in three conditioning trials. The four conditioned stimuli were 100 microM amiloride hydrochloride, water, 0.1 and 0.3 M NaCl. Neither strain demonstrated acquisition of a CTA to amiloride in a brief-access (BA) taste test (5 s trials in the gustometer). Although 0.3 M NaCl is inherently aversive, its pairing with LiCl led to significantly further decreases in licking during the BA test on salt trials in both strains. The D2 strain clearly avoided 0.1 M NaCl, whereas avoidance of this stimulus was more equivocal in B6 mice. The inefficacy of amiloride to serve as a conditioned stimulus in taste aversion learning involving three LiCl pairings suggests that the effects of this ENaC blocker on taste-related behavioral responses to NaCl are likely due to its pharmacological interference with sodium taste transduction.     

The selective serotonin reuptake inhibitor paroxetine does not alter consummatory concentration-dependent licking of prototypical taste stimuli by rats

Serotonin and the 5HT(1A) receptor are expressed in a subset of taste receptor cells, and the 5HT(3) receptor is expressed on afferent fibers innervating taste buds. Exogenous administration of the selective serotonin reuptake inhibitor, paroxetine, has been shown to increase taste sensitivity to stimuli described by humans as sweet and bitter. Serotonergic agonists also decrease food and fluid intake, and it is possible that modulations of serotonin may alter taste-based hedonic responsiveness; alternatively, or in combination, serotonin may interact with physiological state to impact ingestive behavior. In this study, the unconditioned licking of prototypical taste stimuli by rats in brief-access taste tests was assessed following paroxetine administration (0.3-10 mg/kg intraperitoneal). We also measured sucrose licking by rats in different deprivation states after paroxetine (5 mg/kg). In neither experiment did we find any evidence of an effect of paroxetine on licking relative to water to any of the taste stimuli in the brief-access test at doses that decreased food intake. However, in some conditions, paroxetine decreased trials initiated to tastants. Therefore, a systemic increase in serotonin via paroxetine administration can decrease appetitive behavior in brief-access tests but is insufficient to alter taste-guided consummatory behavior.     

Initial licking responses of mice to sweeteners: effects of tas1r3 polymorphisms

Recent studies have established that the T1R3 receptor plays a central role in the taste-mediated ingestive response to sweeteners by mice. First, transgenic mice lacking the gene for T1R3, Tas1r3, show dramatically reduced lick responsiveness to most sweeteners. Second, strains with the taster allele of Tas1r3 (T strains) are more sensitive to low sweetener concentrations than strains with the nontaster allele (NT strains) and consume greater quantities of low- to midrange concentrations of sweeteners during 24-h tests. We asked how Tas1r3 polymorphisms influence the initial licking responses of four T strains (FVB/NJ, SWR/J, SM/J, and C57BL/6J) and four NT strains (BALB/cJ, 129P3/J, DBA/2J, and C3H/HeJ) to two sweeteners (sucrose and SC-45647, an artificial sweetener). We used the initial licking response as a measure of the taste-mediated ingestive response because its brief duration minimizes the potential contribution of nontaste factors (e.g., negative and positive postingestive feedback). Further, we used two complimentary short-term intake tests (the brief-access taste test and a novel 1-min preference test) to reduce the possibility that our findings were an epiphenomenon of a specific testing procedure. In both tests, the T strains were more responsive than the NT strains to low concentrations of each sweetener. At higher concentrations, however, there was considerable overlap between the T and NT strains. In fact, the initial licking response of several NT strains was more vigorous than (or equivalent to) that of several T strains. There was also considerable variation among strains with the same Tas1r3 allele. We conclude that Tas1r3 polymorphisms contribute to strain differences in initial lick responsiveness to low but not high concentrations of sweeteners.