Extensive Lesions in Rat Insular Cortex Significantly Disrupt Taste Sensitivity to NaCl and KCl and Slow Salt Discrimination Learning

While studies of the gustatory cortex (GC) mostly focus on its role in taste aversion learning and memory, the necessity of GC for other fundamental taste-guided behaviors remains largely untested. Here, rats with either excitotoxic lesions targeting GC (n = 26) or sham lesions (n = 14) were assessed for postsurgical retention of a presurgically LiCl-induced conditioned taste aversion (CTA) to 0.1M sucrose using a brief-access taste generalization test in a gustometer. The same animals were then trained in a two-response operant taste detection task and psychophysically tested for their salt (NaCl or KCl) sensitivity. Next, the rats were trained and tested in a NaCl vs. KCl taste discrimination task with concentrations varied. Rats meeting our histological inclusion criterion had large lesions (resulting in a group averaging 80% damage to GC and involving surrounding regions) and showed impaired postsurgical expression of the presurgical CTA (LiCl-injected, n = 9), demonstrated rightward shifts in the NaCl (0.54 log₁₀ shift) and KCl (0.35 log₁₀ shift) psychometric functions, and displayed retarded salt discrimination acquisition (n = 18), but eventually learned and performed the discrimination comparable to sham-operated animals. Interestingly, the degree of deficit between tasks correlated only modestly, if at all, suggesting that idiosyncratic differences in insular cortex lesion topography were the root of the individual differences in the behavioral effects demonstrated here. This latter finding hints at some degree of interanimal variation in the functional topography of insular cortex. Overall, GC appears to be necessary to maintain normal taste sensitivity to NaCl and KCl and for salt discrimination learning. However, higher salt concentrations can be detected and discriminated by rats with extensive damage to GC suggesting that the other resources of the gustatory system are sufficient to maintain partial competence in these tasks, supporting the view that such basic sensory-discriminative taste functions involve distributed processes among central gustatory structures.     

Response properties of macaque monkey chorda tympani fibers

Many of the chorda tympani fibers of crab-eating monkeys respond to more than one of the four basic stimuli (NaCl, sucrose, HCl, and quinine hydrochloride) as well as cooling or warming of the tongue. Fibers could be classified into four categories depending on their best sensitivity to any one of the four basic stimuli. Sucrose-best and quinine-best fibers are rather specifically sensitive to sucrose and quinine, respectively, while salt-best and acid-best fibers respond relatively well to HCl and NaCl, respectively. Saccharin, dulcin, and Pb acetate produce a good response in sucrose-best fibers, but quinine- best and salt-best fibers also respond to saccharin. Highly significant positive correlations exist between amounts of responses to sucrose and those to saccharin, dulcin, and Pb acetate, indicating that these substances produce in the monkey a taste quality similar to that produced by sucrose. Compared with chroda tympani fibers of rats, hamsters, and squirrel monkeys, macaque monkey taste fibers are more narrowly tuned to one of the four basic taste stimuli and more highly developed in sensitivity to various sweet-tasting substances. Also LiCl and NaCl are more effective stimuli for gustatory receptors in macaque monkeys than NH4Cl and KCl. This contrasts with a higher sensitivity to KCl and NH4Cl than to NaCl in chorda tympani fibers of squirrel monkeys.     

Parabrachial unit activities after the acquisition of conditioned taste aversion to a non-preferred HCl solution in rats

Abstract In a behavioral experiment, rats reliably acquired a taste aversion to non-preferred 0.01 M HCl that had been previously paired with intraperitoneal injection of 0.15 M LiCl. These rats showed aversions to other acidic solutions such as malic acid and tartaric acid. In a neurophysiological experiment, the neuronal activities of the parabrachial nucleus (PBN) were recorded after the acquisition of conditioned taste aversion (CTA) to 0.01 M HCl in urethane-anesthetized rats. Neuronal responses to the conditioned stimulus (CS) did not change on the whole but decreased in the dorsal region to the brachium conjunctivum. The proportion of HCl-best to NaCl-best units was lower in the CTA group than in controls. The spontaneous firing rate was lower in the CTA group than in controls. Correlation coefficients between the HCl CS and normally preferred tastes (sucrose and NaCl) were more negative and those between HCl and quinine were more positive in the CTA group than in the controls. These results may be explained by the notion that gustatory responses of PBN neurons are concerned with alterations in taste hedonics after the acquisition of conditioned taste aversions.     

Generalization of conditioned taste aversions in hamsters: evidence for multiple bitter receptor sites

Multiple bitter receptor sites appear to exist within the hamstergustatory system supporting the data of other investigatorson humans, rats and frogs. The sodium salts of four anions,m-nitrobenzene sulfonate (NBSA), picrate, m-nitrobenzoate (NBA)and cholate, were tested in two-bottle preference tests andfor generalization to a variety of stimuli in a conditionedtaste aversion (CTA) paradigm. All four of these anions arebitter to humans. One, NBSA, generalized to sucrose suggestinga sweet taste, while the remaining three appear to be bitterwith varying degrees of saltiness. The bitterness of these threeanions to hamsters appears to be perceptually different froma quinine-type bitterness. Separate bitter receptor sites areindicated for quinine and urea, plus a third site acceptingNBA, picrate and cholate. More bitter sites are plausible. Separatesites for quinine and urea appear to occur across species. Itwas also concluded that quinine does not serve as a prototypicbitter stimulus for all bitters in the CTA test.     

Generalization of specific taste aversions to alcohol in the rat

Two experiments were conducted to examine the taste qualitiesof alcohol in the rat. In Experiment 1, rats were trained toavoid sucrose, quinine or a sucrose + quinine mixture. In Experiment2, rats were trained to avoid sucrose, hydrochloric acid ora sucrose + hydrochloric acid mixture. In both experiments ratswere then tested for generalization to 3, 6 and 9% (v/v) alcoholsolutions. Following the alcohol tests rats were tested withthe taste solutions used during training. Results showed thatrats trained to avoid sucrose (Experiments 1 and 2), quinineor the sucrose + quinine mixture generalized that aversion tothe 6% alcohol solution. No generalization was found to the3% alcohol solution. No generalization was displayed by ratstrained to avoid either the hydrochloric acid solution or thesucrose + hydrochloric acid solution. Following the alcoholtests, all trained rats exhibited strong aversions to the solutionthey were trained to avoid. In addition, rats trained to avoida single solution generalized that aversion to the mixture andrats trained to avoid a mixture generalized to the single components.     

Reduction of saltiness and bitterness after a chlorhexidine rinse

Chronic rinsing with chlorhexidine, an oral-antiseptic, has been shown to decrease the saltiness of NaCl and the bitterness of quinine. The effect of acute chlorhexidine on taste has not been investigated. The purpose of the present study was to examine the effect of acute chlorhexidine rinses on taste intensity and quality of 11 stimuli representing sweet, salt, sour, bitter and savory. All stimuli were first matched for overall intensity so the effects of chlorhexidine would be directly comparable across compounds. As a control treatment, the bitter taste of chlorhexidine digluconate (0.12%) was matched in intensity to quinine HCl, which was found to cross-adapt the bitterness of chlorhexidine. Subjects participated in four experimental conditions: a pre-test, a quinine treatment, a chlorhexidine treatment, and a post-test condition, while rating total taste intensity and taste qualities in separate test sessions. Relative to the quinine treatment, chlorhexidine was found to decrease the salty taste of NaCl, KCl and NH4Cl, and not to significantly affect the tastes of sucrose, monosodium glutamate (MSG), citric acid, HCl and the taste of water. The bitter taste of urea, sucrose octa-acetate and quinine were suppressed after chlorhexidine rinses relative to water rinses, but were only marginally suppressed relative to quinine rinses. Potential mechanisms are discussed.     

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.     

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.     

An Analysis of Hamster Afferent Taste Nerve Response Functions

Sensitivities to moderately intense stimuli representing four taste qualities to man were determined for 79 hamster chorda tympani fibers. Some fibers were very sensitive to sucrose, sodium chloride, or hydrochloric acid, but none were very sensitive to quinine. These sensitivities were not randomly distributed among fibers: the sucrose sensitivity was separated from and negatively correlated with the other sensitivities which were associated and positively correlated with each other. Moreover, there were a limited number of sensitivity patterns: (a) fibers responding best to sucrose responded second-best to salt, less to acid, not to quinine; (b) fibers responding best to salt either responded second-best to sucrose and not to acid or quinine; or second-best to acid, less to quinine, and not to sucrose; and (c) fibers responding best to acid responded second-best to salt, more to quinine, and less to sucrose than other fibers. Therefore, if four stimuli of different taste qualities are ordered from acceptable to unacceptable, neural response functions of most hamster chorda tympani taste fibers peak at one point. Sensitivities to nine other moderately intense stimuli which vary in quality to man were also determined for 46–49 of the fibers. Sensitivities to sweet stimuli were always associated with each other and separated from sensitivities to nonsweet stimuli. Sensitivities to nonsweet stimuli were all associated with each other; however, the strongest correlations were between sensitivities to stimuli of like quality, e.g., the three acids or the two sodium salts.     

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.     

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.     

Conductance Change Associated with Receptor Potentials of Gustatory Cells in Rat

The electrical properties of gustatory cells and cells which do not respond to chemical stimuli in the taste bud of fungiform papillae in rats were studied by means of intracellular microelectrodes. Neither of these cell types showed spike electrogenesis. Gustatory cells showed a depolarization, the receptor potential, associated with an increase in the membrane conductance in response to NaCl, sucrose, and HCl, whereas quinine produced a decrease in the conductance together with an increase in the receptor potential magnitude. The reversal point of the receptor potential in response to NaCl or KCl was close to zero membrane potential, but in the case of quinine it was at a more negative potential level than the resting potential. From these results two receptive processes are postulated in the gustatory cell membrane. When the gustatory cells were stimulated for a long duration by concentrated NaCl or sucrose, receptor potentials showed adaptation with decrease in magnitude, but adaptation of the responses to HCl and quinine were hardly detected. Adaptation of the receptor potential was not correlated with conductance change.     

Glossopharyngeal nerve transection does not alter taste reactivity to sucrose conditioned to be aversive

Glossopharyngeal nerve (GL) transection in rats is known to markedly reduce gaping, a stereotypical aversive oromotor behavior, in response to intraorally delivered quinine. In this experiment we tested whether GL transection would reduce gaping in response to an otherwise palatable stimulus (sucrose) but conditioned to be aversive. Sprague-Dawley rats were implanted with intraoral cannulae. Five received bilateral transection of the GL and five served as sham-operated controls. Water-deprived rats were presented with 0.3 M sucrose for 15 min immediately followed by an injection of 0.15 M LiCl on three occasions. Rats were then habituated to the taste reactivity chamber and intraoral fluid infusion for 3 days, and tested on day 4 with a 1 ml infusion (1 min) of 0.3 M sucrose. All rats drank negligible amounts of sucrose by the third conditioning session and there were no differences in sucrose intake between the groups. There were no significant differences in gapes, or any other measured oromotor response, to sucrose between GL-transected and sham-operated rats. These results show that the GL is not a necessary afferent limb for gaping in response to conditionally aversive taste compounds.     

Diazepam-binding inhibitor-like activity in rat cerebrospinal fluid after stimulation by an aversive quinine taste

Cerebrospinal fluid (CSF) taken from rats after stimulation by an aversive quinine taste (hereafter called quinine CSF) administered into the fourth ventricle of mice suppressed their intake of 5% sucrose solution. We examined the effects of CSF on glutathione-induced tentacle ball formation (TBF) of hydra to determine the change in CSF components associated with aversive taste stimuli. The suppressive activity of quinine CSF on TBF in the presence of 3 microM S:-methyl-glutathione (GSM) was markedly lower than that of CSF obtained from control rats (control CSF). Pronase-treated quinine CSF had suppressive activity similar to that of control CSF. The active principle passed through an ultrafiltration membrane, with a molecular weight cut-off of 30 kDa, but not through one with a cut-off of 3 kDa. A peptide fragment of diazepam-binding inhibitor (DBI) nullified the suppression of TBF at 3 microM GSM by control CSF. The nullifying activity of quinine CSF was not observed after treatment with a benzodiazepine receptor preparation that was able to bind DBI. When flumazenil, a benzodiazepine receptor antagonist, was given to mice, the suppression of the intake of 5% sucrose solution by quinine CSF was partially reversed. It is suggested that quinine CSF contains a DBI-like substance.     

Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output

The nucleus accumbens (NAc) is a key component of the brain's reward pathway, yet little is known of how NAc cells respond to primary rewarding or aversive stimuli. Here, naive rats received brief intraoral infusions of sucrose and quinine paired with cues in a classical conditioning paradigm while the electrophysiological activity of individual NAc neurons was recorded. NAc neurons (102) were typically inhibited by sucrose (39 of 52, 75%) or excited by quinine (30 of 40, 75%) infusions. Changes in firing rate were correlated with the oromotor response to intraoral infusions. Most taste-responsive neurons responded to only one of the stimuli. NAc neurons developed responses to the cues paired with sucrose and quinine. Thus, NAc neurons are innately tuned to rewarding and aversive stimuli and rapidly develop responses to predictive cues. The results indicate that the output of the NAc is very different when rats taste rewarding versus aversive stimuli.     

Learned aversions and taste qualities in hamsters

Interralations among taste perceptions in gloden hamsters (Mesocricetusauratus) were examined using generalizaions of learned tasteaversions. If stimulus A is avoided given a taste aversion hasbeen established to stimulus B, and vice versa, A and B ‘cross-generalize’.Stimuli within five groups cross-generalized. The groups ofcompounds were (i) sweeteners (fructose, saccharin, sucrose);(ii) sodium salts (NaCl, NaNO₃, Na₂SO₄): (iii) non-sodium salts(KCl, MgSO₄ NH₄Cl) plus quinine HCl; (iv) acids (acetic, hydrochloric,citric); and (v) urea. Only two pairs of stimuli from differentgroups cross-generalized (HCl—NH₄Cl. quinine HCl—urea).Neural patterns of response recorded form chorda tympam nervefibers in hamsters suggest that taste receptors on the anteriortongue distinguish among three groups of taste stimuli: sweeteners,sodium salts, and a group including non-sodium salts, acids,quinine HCl and urea. Neurons innervating other taste fieldsare likely to provide the information that hamsters use to discriminateamong the tastes of non-sodium-salt and non-sweetener stimuli.     

Taste responses of the gerbil IXth nerve

Summated taste responses to 12 taste solutions were recordedfrom the IXth (glossopharyngeal) nerve of 38 Mongolian gerbils(Meriones unguiculatus). 0.3 M NH₄Cl was the most effectivestimulant. The relative magnitude of the peak summated responsewas a positively accelerated function of log molar concentration.Absolute thresholds were determined for three chemicals: 0.002M NaCl, 0.0003 M HCl, and 0.002 M sucrose. The relative magnitudesof the responses to quinine, NH₄Cl, and KCl were greater forthe IXth nerve than for the chorda tympani nerve, whereas NaClwas more effective for the chorda tympani. A similar patternis seen in the rat. Acetic and citric acid may bind to commonreceptor sites. NH₄Cl, KCl, and HCl may also have receptor sitesin common.     

Ontogenetic characteristics of the acquisition and extinction of a taste aversion in dogs following damage to the dorsal area of the hippocampus

In 2-9 months dogs the influence was studied of ablation of the hippocampus dorsal area on formation and preservation of conditioned taste aversion (CTA), elaborated by combination of 30% sucrose solution with i.p. injection of 0.28 M LiCl solution. Lesion of the hippocampus dorsal area does not prevent acquisition after the first pairing of conditioned taste aversion in puppies and adult dogs. Heterogeneous influences are observed after hippocampus lesions on the process of CTA extinction in animals of different ages. Acquaintance with conditioned stimulus before CTA acquisition accelerates the process of its extinction in hippocampectomized indiviuals, but less than in animals with an intact hippocampus.     

Amiloride alters lick rate responses to NaCl and KCl in rats

The role-of cation channels on taste cell membranes to salttaste sensation was assessed in rats. We measured the numberof licks during multiple 10-s presentations of NaCl and KClconcentrations (0.05, 0.09, 0.16, 0.28, 0.5 M) dissolved ineither water or in 100 µM amiloride, a sodium-channelblocker. The number of licks to water and 0.3 M sucrose wasalso measured. The number of licks to NaCl was significantlylower and the number of licks to KCl was significantly higherwhen these test solutions were dissolved in amiloride than inwater. There were no differences in lick responses to waterand sucrose. These results suggest that amiloride may have alteredthe taste of NaCl and KCl. The results are discussed in relationshipto prior electrophysiological studies characterizing the effectof amiloride in blocking salt responses of the chorda tympaninerve.     

The taste characteristics of sodium-saccharin in the rat: a re-examination of the dual taste hypothesis

A conditioned flavor aversion (CFA) was used to measure thetaste characteristics of 0.005 and 0.025 M Na-saccharin in therat. At neither concentration did the rats show generalizationto NaCl, quinine HCl or SO₄, sucrose octa-acetate or HCl, whereasgeneralization to sucrose was found at both concentrations.When the CFA was formed to 0.0001 M quinine HCl, no direct evidencewas found for generalization of the aversion to either saccharinconcentration. Thus at the two concentrations used Na-saccharinwould appear to be primarily sucrose-like in the rat taste systemwhen behavioral criteria are used.