Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal "bitter taste" cue

The discovery that cells in the gastrointestinal (GI) tract express the same molecular receptors and intracellular signaling components known to be involved in taste has generated great interest in potential functions of such post-oral "taste" receptors in the control of food intake. To determine whether taste cues in the GI tract are detected and can directly influence behavior, the present study used a microbehavioral analysis of intake, in which rats drank from lickometers that were programmed to simultaneously deliver a brief yoked infusion of a taste stimulus to the intestines. Specifically, in daily 30-min sessions, thirsty rats with indwelling intraduodenal catheters were trained to drink hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M NaCl solution. Once trained, in a subsequent series of intestinal taste probe trials, rats reduced licking during a 6-min infusion period, when a bitter stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for infusion, apparently conditioning a mild taste aversion. Presentation of the DB in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the development of the response across trials and strengthened the temporal resolution of the early licking suppression in response to the arrival of the DB in the intestine. In an experiment to evaluate whether CCK is involved as a paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist devazepide partially blocked the response to intestinal DB. In contrast to their ability to detect and avoid the bitter taste in the intestine, rats did not modify their licking to saccharin intraduodenal probe infusions. The intestinal taste aversion paradigm developed here provides a sensitive and effective protocol for evaluating which tastants-and concentrations of tastants-in the lumen of the gut can control ingestion.     

The taste of polycose in hamsters

Hamsters show a preference for Polycose, a mixture of starch-derived glucose polymers, that is as strong as their preference for sucrose. However, in the hamster, taste aversions to Polycose may be less easily acquired than taste aversions to sucrose and the qualitative aspects of Polycose are unknown in this species. In order to examine the taste of Polycose in the hamster, we utilized a taste-aversion protocol with two conditioning trials. Animals were trained to avoid one of three different conditioning stimuli: 50 mM sucrose, 100 mM Polycose and a mixture of 50 mM sucrose with 100 mM Polycose. Control animals were conditioned with deionized water. After the second conditioning trial, generalization testing began for the three conditioning stimuli plus 3 mM citric acid, 300 mM KCI and 30 mM NaCl. The results showed that aversions to Polycose, sucrose or the Polycose/sucrose mixture cross- generalized, demonstrating that Polycose and sucrose share a common taste percept in the hamster. None of the aversions generalized to NaCl, citric acid or KCI. In addition, comparisons among the patterns of taste generalizations indicated that the tastes of Polycose and sucrose also had distinct qualitative components. Finally, although the taste of 100 mM Polycose was more salient than the taste of 50 mM sucrose, the taste of sucrose could still be detected in a mixture with Polycose.      

Greater superficial petrosal nerve transection in rats does not change unconditioned licking responses to putatively sweet taste stimuli

The greater superficial petrosal nerve (GSP), innervating taste buds in the palate, is known to be exceptionally responsive to sucrose, especially compared with the responsiveness of the chorda tympani nerve (CT). However, whereas transection of the CT (CTX) alone has little or no effect on unconditioned licking responses to many "sweet" stimuli, the impact of GSP transection (GSPX) alone is equivocal. To further examine the role of the GSP on licking responses to putatively sweet-tasting substances, brief-access taste tests were conducted in nondeprived rats before and after sham surgery (SHAM) or CTX or GSPX. A range of concentrations of sucrose, L-alanine, glycine, and L-serine, with and without 1.0 mM inosine monophosphate (IMP) added, were used. All groups showed significant concentration-dependent increases in licking to all stimuli presurgically and postsurgically. CTX decreased licking responses relative to SHAM rats in the first sucrose test. There was also a group x concentration interaction for L-alanine, but post hoc tests did not reveal its basis. Other than this, there were no significant differences among the surgical groups. Interestingly, rats with GSPX tended to initiate fewer trials than SHAM rats. Overall, after GSPX, the remaining gustatory nerves are apparently sufficient to maintain concentration-dependent licking responses to all stimuli tested here. The disparity between our results and others in the literature where GSPX reduced licking responses to sucrose is possibly related to differences in surgical technique or test trial duration.     

Anatomical dissociation of melanocortin receptor agonist effects on taste- and gut-sensitive feeding processes

Injections of the melanocortin 3/4 receptor (MCR) agonist melanotan II (MTII) to a variety of brain structures produces anorexia, suggesting distributed brain MCR control of food intake. We performed a detailed analysis of feeding behavior (licking microstructure analysis) after a range of MTII doses (0.005 nM to 1 nM) was targeted to the forebrain (third ventricle, 3V) or hindbrain (fourth ventricle, 4V) regions. MTII (0.1 nM and 1 nM) delivered to the 3V or 4V significantly reduced 0.8 M sucrose intake. The anorexia was mediated by reductions in the number of licking bursts in the meal, intrameal ingestion rate, and meal duration; these measures have been associated with postingestive feedback inhibition of feeding. Anorexia after 3V but not 4V MTII injection was also associated with a reduced rate of licking in the first minute (initial lick rate) and reduced mean duration of licking bursts; these measures have been associated with taste evaluation. MTII effects on taste evaluation were further explored: In experiment 2, 3V MTII (1 nM) significantly reduced intake of noncaloric 4 mM saccharin and 0.1 M and 1 M sucrose solutions, but not water. The anorexia was again associated with reduced number of licking bursts, ingestion rate, meal duration, initial lick rate, and mean burst duration. In experiments 3 and 4, brief access (20 s) licking responses for sweet sucrose (0.015 M to 0.25 M) and bitter quinine hydrochloride (0.01 mM to 1 mM) solutions were evaluated. Licking responses for sucrose were suppressed, whereas those for quinine solutions were increased after 3V MTII, but not after 4V MTII injections (0.1 nM and 1 nM). The results suggest that multiple brain MCR sites influence sensitivity to visceral feedback, whereas forebrain MCR stimulation is necessary to influence taste responsiveness, possibly through attenuation of the perceived intensity of taste stimuli.     

The sweet-bitter taste of alcohol: aversion generalization to various sweet-quinine mixtures in the rat

Rats were trained to avoid a 5% alcohol solution and then testedwith either sweet + quinine hydrochloride solutions (Experiment1) or sweet + hydrochloric acid solutions (Experiment 2). Thesweet stimuli used were sucrose, glucose, fructose and saccharin.Significant aversion generalization was found only in Experiment1 where trained rats generalized to all four test stimuli, thussuggesting that alcohol has a sweet taste (in combination withbitter) not specific to one sweetener. No significant aversiongeneralization was noted in Experiment 2 when sweet + hydrochloricacid solutions were tested. In Experiment 3, rats were trainedto avoid 6% alcohol and tested with sucrose + quinine hydrochloridemixtures with varying concentrations of each component. In general,rats showed generalization of the alcohol aversions across thevarious concentrations of sucrose and quinine hydrochloridetested.     

Monosodium glutamate and sweet taste: discrimination between the tastes of sweet stimuli and glutamate in rats

Generalization of a conditioned taste aversion (CTA) is based on similarities in taste qualities shared by the aversive substance and another taste substance. CTA experiments with rats have found that an aversion to a variety of sweet stimuli will cross-generalize with monosodium glutamate (MSG) when amiloride, a sodium channel blocker, is added to all solutions to reduce the taste of sodium. These findings suggest that the glutamate anion elicits a sweet taste sensation in rats. CTA experiments, however, generally do not indicate whether two substances have different taste qualities. In this study, discrimination methods in which rats focused on perceptual differences were used to determine if they could distinguish between the tastes of MSG and four sweet substances. As expected, rats readily discriminated between two natural sugars (sucrose, glucose) and two artificial sweeteners (saccharin, SC45647). Rats also easily discriminated between MSG and glucose, saccharin and, to a lesser extent, SC45647 when the taste of the sodium ion of MSG was reduced by the addition of amiloride to all solutions, or the addition of amiloride to all solutions and NaCl to each sweet stimulus to match the concentration of Na+ in the MSG solutions. In contrast, reducing the cue function of the Na+ ion significantly decreased their ability to discriminate between sucrose and MSG. These results suggest that the sweet qualities of glutamate taste is not as dominate a component of glutamate taste as CTA experiments suggest and these qualities are most closely related to the taste qualities of sucrose. The findings of this study, in conjunction with other research, suggest that sweet and umami afferent signaling may converge through a taste receptor with a high affinity for glutamate and sucrose or a downstream transduction mechanism. These data also suggest that rats do not necessarily perceive the tastes of these sweet stimuli as similar and that these sweet stimuli are detected by multiple sweet receptors.     

The taste of alcohol for rats as revealed by aversion generalization tests

In six experiments, naive rats were trained to avoid alcoholby pairing its presentation with lithium chloride-induced illness.Rats were then tested for aversion generalization by presentingvarious test solutions. Rats trained to avoid either 3, 6 or9% (v/v) alcohol generalized the aversion to a sucrose + quininehydrochloride solution. The five remaining binary combinationsof sucrose, sodium chloride, hydrochloric acid and quinine hydrochloridefailed to produce significant generalization in trained rats(Experiment 1). In further experiments, rats trained to avoid6% alcohol showed significant aversion generalization to a varietyof sucrose + other ‘bitter’ solutions (Experiment2) and sucrose + acid solutions (Experiment 3). Varying theconcentration of hydrochloric acid in a sucrose + acid mixtureproduced small but uniform degrees of aversion generalization(Experiment 4). Rats trained to avoid 6% alcohol did not generalizethe aversion to sucrose alone, regardless of concentration (Experiment5). Finally, in Experiment 6, rats trained to avoid 6% alcoholsuppressed consumption over a range of alcohol concentrations.These results confirm that, for rats, the taste of alcohol hasa complex set of characteristics; sweet taste in combinationwith other tastes appears to be the most similar as it is tothese solutions that rats with alcohol aversions show the mostgeneralized avoidance.     

Discrimination between the tastes of sucrose and monosodium glutamate in rats

Conditioned taste aversion studies have demonstrated that rats conditioned to avoid monosodium glutamate (MSG) with amiloride added to reduce the intensity of the sodium component of MSG taste, will generalize an aversion for MSG to sucrose and vice versa. This suggests that taste transduction for sodium, sucrose and MSG may intersect at some point. Generalization of conditioned taste aversion indicates that two substances share similar taste features, but it does not reveal the extent of their differences. In this study, we tested how well rats can discriminate sucrose and MSG under a variety of conditions. Water-deprived rats were trained on a combination of water reinforcement and shock avoidance to discriminate between MSG and sucrose, both with and without amiloride, and with and without equimolar NaCl in all solutions. In the absence of amiloride, rats reliably distinguished between MSG and sucrose down to 10 mM solutions. However, they could correctly identify solutions only above 50 mM in the presence of amiloride, equimolar sodium chloride, or both. These results suggest that gustatory stimulation by MSG and sucrose interact somewhere in taste transduction, perhaps within taste receptor cells or gustatory afferent pathways.     

Is glycine "sweet" to mice? Mouse strain differences in perception of glycine taste

Glycine is an amino acid tasting sweet to humans. In 2-bottle tests, C57BL/6ByJ (B6) mice strongly prefer glycine solutions, whereas 129P3/J (129) mice do not, suggesting that they differ in perception of glycine taste. We examined this question using the conditioned taste aversion (CTA) generalization technique. CTA was achieved by injecting LiCl after drinking glycine, and next its generalization to 10 taste solutions (glycine, sucrose, saccharin, D-tryptophan, L-tryptophan, L-alanine, L-proline, L-glutamine, NaCl, and HCl) was examined by video recording licking behavior. Both B6 and 129 mice generalized the aversion to sucrose, saccharin, L-alanine, and L-proline and did not generalize it to NaCl, HCl, and L-tryptophan. This indicates that both B6 and 129 mice perceive the sweetness (i.e., a sucrose-like taste) of glycine. Thus, the lack of a glycine preference by 129 mice cannot be explained by their inability to perceive its sweetness. Strain differences were observed for CTA generalization to 2 amino acids: 129 mice generalized aversion to L-glutamine but not D-tryptophan, whereas B6 mice generalized it to D-tryptophan but not L-glutamine. 129.B6-Tas1r3 congenic mice with 2 genotypes of the Tas1r3 locus (B6/129 heterozygotes and 129/129 homozygotes) did not differ in aversion generalization, suggesting that the differences between 129 and B6 strains are not attributed to the Tas1r3 allelic variants and that other, yet unknown, genes are involved in taste perception of amino acids.     

咸味觉厌恶模型大鼠鼓索神经对味觉刺激的电生理反应特性

目的:探索大鼠咸味觉厌恶建立后外周鼓索神经(CT)对咸味觉及其他味觉刺激的电生理反应特性的改变。方法:将14只SD成年雄性大鼠分为咸味觉厌恶模型组(CTA)和对照组(n=7/group)。实验第1日给予大鼠30min的0.1mol/LNaCl饮食,随后CTA组和对照组大鼠分别腹腔注射2ml0.15mol/LLiCl和同等量生理盐水。在第2、3和4日,测量两组大鼠每天30min内对NaCl和蒸馏水饮用量。于第4日行为学测试后,分别记录CTA组大鼠和对照组大鼠CT对口内给予系列浓度NaCl溶液、0.3mol/LNaCl与0.1mmol/L阿米洛利(一种舌上皮钠通道阻断剂)混合液和其他四种基本味觉刺激溶液的电生理反应。结果:与对照组相比,CTA组大鼠CT对系列浓度NaCl和其他4种基本味觉刺激的电生理反应特性没有发生明显变化(P>0.05);舌上皮钠通道阻断剂阿米洛利强烈抑制CTA大鼠对NaCl的反应(P<0.01)。结论:条件性咸味觉厌恶模型大鼠CT对各种味觉刺激的电生理反应特性没有发生明显改变。     

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.     

Taste, salience, and increased NaCl ingestion after repeated sodium depletions

Previous studies have shown that repeated sodium depletions using the natriuretic-diuretic furosemide induce progressive increases in NaCl ingestion. We investigated the role of taste in this behavioral sensitization in Sprague-Dawley rats using short-term lickometer testing along with 2-h stimulated intake tests. Our results show maximal licking across a range of NaCl concentrations after each of the three depletions, regardless of whether the solutions contained sucrose or were presented alone. Similarly, the presence of sucrose did not affect stimulated NaCl intake in long-term tests, although ingestion of NaCl solutions increased progressively with successive depletions. Finally, both licking and ingestion returned to baseline levels during need-free conditions. These results suggest that sodium imbalance acutely increases the salience of sodium taste and thereby the likelihood of NaCl ingestion, which may, in turn, contribute to progressive increases in NaCl intake that occur with multiple furosemide-induced sodium depletions.     

A High Throughput In Vivo Assay for Taste Quality and Palatability

Taste quality and palatability are two of the most important properties measured in the evaluation of taste stimuli. Human panels can report both aspects, but are of limited experimental flexibility and throughput capacity. Relatively efficient animal models for taste evaluation have been developed, but each of them is designed to measure either taste quality or palatability as independent experimental endpoints. We present here a new apparatus and method for high throughput quantification of both taste quality and palatability using rats in an operant taste discrimination paradigm. Cohorts of four rats were trained in a modified operant chamber to sample taste stimuli by licking solutions from a 96-well plate that moved in a randomized pattern beneath the chamber floor. As a rat’s tongue entered the well it disrupted a laser beam projecting across the top of the 96-well plate, consequently producing two retractable levers that operated a pellet dispenser. The taste of sucrose was associated with food reinforcement by presses on a sucrose-designated lever, whereas the taste of water and other basic tastes were associated with the alternative lever. Each disruption of the laser was counted as a lick. Using this procedure, rats were trained to discriminate 100 mM sucrose from water, quinine, citric acid, and NaCl with 90-100% accuracy. Palatability was determined by the number of licks per trial and, due to intermediate rates of licking for water, was quantifiable along the entire spectrum of appetitiveness to aversiveness. All 96 samples were evaluated within 90 minute test sessions with no evidence of desensitization or fatigue. The technology is capable of generating multiple concentration–response functions within a single session, is suitable for in vivo primary screening of tastant libraries, and potentially can be used to evaluate stimuli for any taste system.     

Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced suppression of intake

Ondansetron, a selective serotonin-type 3 (5-HT(3)) receptor antagonist, was used to test the hypothesis that duodenal infusion of isosmotic solutions of Polycose or its hydrolytic product glucose suppressed intake through 5-HT(3) receptors. Polycose suppressed sucrose intake across both concentrations infused (132 mM, 7.6 +/- 0.6 ml; 263 mM, 2.3 +/- 0.5 ml), compared with intake under control conditions (12.6 +/- 0.3 ml, P <0.001). Pretreatment with 1.0 mg/kg ondansetron attenuated reduction of sucrose intake induced only by the highest concentration of Polycose (4.6 +/- 0.8 ml, P = 0.004). Dose-response testing revealed that suppression of food intake by 263 mM Polycose was equally attenuated by ondansetron administered at 1.0, 2.0, and 5.0 mg/kg but not when given at 0.125, 0.25, and 0.5 mg/kg. Acarbose, an alpha-glucosidase inhibitor, attenuated Polycose-induced suppression of food intake, and pretreatment with 1.0 mg/kg ondansetron had no further effect. Suppression of intake after 990 mM glucose but not mannitol infusion was attenuated by pretreatment with 1.0 mg/kg ondansetron. The competitive SGLT(1) inhibitor, phloridzin, had no effect on 60-min 990 mM glucose-induced suppression of intake or the ability of ondansetron to attenuate this suppression of intake. Conversely, glucose-induced suppression of intake was attenuated by phloridzin at earlier time points and further attenuated when rats were pretreated with 1.0 mg/kg ondansetron. Ondansetron administration alone had no effect on intake at any dose tested. We conclude that 5-HT(3) receptors participate in the inhibition of food intake by intraduodenal infusion of carbohydrate solutions through a posthydrolytic, preabsorptive mechanism.     

Citric acid and quinine share perceived chemosensory features making oral discrimination difficult in C57BL/6J mice

Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical.     

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.     

Serotonin-type 3 receptors mediate intestinal lipid-induced satiation and Fos-like immunoreactivity in the dorsal hindbrain

Several gastrointestinal stimuli, including some intestinal nutrients, have been shown to exert their satiating effect via activation of serotonin type-3 (5-HT(3)) receptors. The presence of lipids in the small intestine potently suppresses food intake; however, whether 5-HT(3) receptors play a role in this response has not been directly examined. Therefore, using the selective 5-HT(3) receptor antagonist ondansetron, we tested the hypothesis that duodenal infusion of lipid suppresses intake of both sucrose solution and chow through 5-HT(3) receptor activation. Rats duodenally infused with 72 and 130 mM Intralipid suppressed 1-h 15% sucrose intake by 33 and 67%, respectively. Suppression of sucrose intake by 72 mM Intralipid was significantly attenuated by ondansetron at all doses tested (0.5, 1.0, 2.0, and 5.0 mg/kg ip), whereas the lowest effective dose of ondansetron to attenuate suppression of intake by 130 mM Intralipid was 1.0 mg/kg. Furthermore, infusion of 130 mM Intralipid suppressed 1- and 4-h chow intake by 35 and 20%, respectively. Ondansetron administered as low as 0.5 mg/kg significantly attenuated 1-h Intralipid-induced suppression of chow intake and completely reversed the suppression by 4 h. Administration of ondansetron alone did not alter sucrose or chow intake compared with vehicle injection at any time. Finally, to test whether Intralipid-induced neuronal activation of the dorsal vagal complex is mediated by 5-HT(3) receptors, Fos-like immunoreactivity (Fos-LI) was quantified in ondansetron-pretreated rats following intestinal lipid infusion. Ondansetron (1 mg/kg) significantly attenuated duodenal intralipid-induced Fos-LI in the dorsal hindbrain. These data support the hypothesis that 5-HT(3) receptors mediate both satiation, as well as hindbrain neuronal responses evoked by intestinal lipids.     

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.     

The taste of monosodium glutamate (MSG), L-aspartic acid, and N-methyl-D-aspartate (NMDA) in rats: are NMDA receptors involved in MSG taste?

Monosodium glutamate (MSG) is believed to elicit a unique taste perception known as umami. We have used conditioned taste aversion assays in rats to compare taste responses elicited by the glutamate receptor agonists MSG, L-aspartic acid (L-Asp), and N-methyl-D-aspartate (NMDA), and to determine if these compounds share a common taste quality. This information could shed new light upon the receptor mechanisms of glutamate taste transduction. Taste aversions to either MSG, L-Asp or NMDA were produced by injecting rats with LiCl after they had ingested one of these stimuli. Subsequently, rats were tested to determine whether they would ingest any of the above compounds. The results clearly show that a conditioned aversion to MSG generalized to L-Asp in a dose-dependent manner. Conversely, rats conditioned to avoid L-Asp also avoided MSG. Conditioned aversions to MSG or L-Asp generalized to sucrose when amiloride was included in all solutions. Importantly, aversions to MSG or L-Asp did not generalize to NMDA, NaCl or KCl, and aversions to NMDA did not generalize to MSG, L-Asp, sucrose or KCl. These data indicate that rats perceive MSG and L-Asp as similar tastes, whereas NMDA, NaCl and KCl elicit other tastes. The results do not support a dominant role for the NMDA subtype of glutamate receptors in taste transduction for MSG (i.e. umami) in rats.     

Electrophysiological analysis of retrieval of conditioned taste aversion in rats. Unit activity changes in critical brain regions.

Gustatory discrimination testing shows that rats with an overtrained conditioned taste aversion (CTA) to isotonic LiCl stop salt intake after 1 to 2 licks at the LiCl spout and move to the adjacent water spout within 0.7 s. Activity of 526 neurones from the nucleus of the solitary tract, gustatory thalamus, gustatory cortex, lateral and ventromedial thalamus, and amygdala was recorded in naive or CTA trained rats during the above gustatory discrimination. Post-stimulus histograms (PSH) triggered by water or salt licks or by spout switching were plotted for single units. Population responses of various regions were obtained by integration of the statistically significant excitatory and inhibitory intervals in the individual PSHs. Lick related changes of unit activity were orserved in 52% and 65% of neurones in control and CTA trained rats, respectively. The CTA training increased the incidence of units in which salt licking influenced the activity less than water licking. Presentation of the aversive fluid induced inhibition of unit activity in the gustatory cortex, ventromedial hypothalamus, and amygdala and excitation in the lateral hypothalamus. The changes started 100 to 150 ms after spout switching and culminated 100 ms later. Activity of the solitary tract nucleus and gustatory thalamus was affected less consistently. The results indicate that the gustatory cortex, amygdala and hypothalamus participate in CTA retrieval but a more specific identification of the electrical correlates of memory readout and of drinking control was not possible.