Phenylthiocarbamide produces conditioned taste aversions in mice

Previous work has demonstrated that SWR/J (SW) mice avoid phenylthiocarbamide (PTC) to a greater degree than C3HeB/FeJ mice in 48 h, two-bottle preference tests given in ascending series. The authors hypothesized, based also on previous work, that SW mice might form a conditioned taste aversion over time due to the toxic properties of PTC. We directly tested this hypothesis by attempting to condition a taste aversion to sucrose by injections of PTC. In experiment 1, PTC was nearly as effective as a strong dose of LiCl in reducing sucrose drinking. In experiment 2, the sucrose aversions were parametrically modified by both sucrose concentration and PTC dose, a hallmark of conditioned taste aversion. We conclude that PTC can cause a conditioned taste aversion and discuss the importance of considering toxic effects of aversive tastants when analyzing behavioral strain differences.     

Attenuation of radiation- and drug-induced conditioned taste aversions following area postrema lesions in the rat

The effects of lesions of the area postrema on the acquisition of radiation- and drug-induced (histamine and lithium chloride) conditioned taste aversions were investigated. The results indicated that area postrema lesions caused a significant attenuation of the aversion produced by pairing a novel sucrose solution with radiation (100 rad) or drug injection. Further, the area postrema lesions produced a similar level of attenuation of the taste aversion in all three treatment conditions. The results are discussed in terms of the implications of this finding for defining the mechanisms by which exposure to ionizing radiation can lead to the acquisition of a conditioned taste aversion.     

Differences in the taste quality of maltose and sucrose in rats: issues involving the generalization of conditioned taste aversions

The present study employed a conditioned taste aversion generalizationparadigm to test the hypothesis that maltose produces tastesensations in the rat which are qualitatively distinguishablefrom sucrose. Since stimulus generalization can occur in boththe quality and intensity domains, an intrachemical (acrossconcentration) generalization gradient was established to aidin the interpretation of the interchemical (across molecules)generalization gradient. Moreover, since the commonly used intaketest is vulnerable to nontaste post-ingestional influences,the present study measured immediate responses to 100 µlstimulus samples, thus increasing our confidence that the behaviorwas under orosensory control. In Experiment 1, naive water deprivedrats were trained in a specially designed gustometer to maintaindrinking-spout contact for intermittent water reinforcement.Following this, rats in the experimental group were given threeexposures to 0.1 M sucrose on separate days, with the firsttwo exposures immediately preceding an injection of LiCl. Acontrol group was treated identically but received distilledwater instead of sucrose. Rats were then tested in the gustometerfor their avoidance of three equimolar concentrations of sucroseand maltose. Rats received ten trials of each stimulus quasi-randomlypresented in two sessions. Results indicated that all sucroseconcentrations were avoided (in experimental group only), butonly the 0.3 M concentration of maltose was avoided. The lowestsucrose concentration was significantly less avoided than thehigher concentrations. Intensity generalization gradients aresuch that intensities weaker than the conditioned stimulus (CS)produce just as much or less of a conditioned response (CR)and intensities stronger than the CS produce just as much ora greater CR than that elicited by the CS itself. Therefore,based on the results of Experimental, it was predicted thatif 0.1 M maltose served as the CS, the order of avoidance shouldbe: 0.3 M sucrose 0.1 M sucrose 0.03 M sucrose 0.3 M maltose 0.1 M maltose 0.03 M maltose, if it were true that maltoseand sucrose produce identical sensations that differ only inintensity. Experiment 2 explicitly tested this prediction usingthe same procedure as Experiment 1 except that 0.1 M maltoseserved as the CS. The observed order of avoidance was 0.3 Mmaltose > 0.1 M maltose > 0.03 M maltose = 0.3 M sucrose= 0.1 M sucrose = 0.03 M sucrose. In both experiments the intrachemicalgeneralization gradient broadened and the interchemical generalizationgradient steepened upon retesting. In conclusion, qualitativedifferences between maltose and sucrose explain the outcomesof these experiments better than differences in the relativeintensity of these sugars at isomolar concentrations.     

Estradiol accelerates extinction of lithium chloride-induced conditioned taste aversions through its illness-associated properties

Estradiol accelerates extinction of LiCl-induced conditioned taste aversions when it is present during a period that starts 2-3 days after acquisition and extends throughout extinction (before and during extinction). It has been suggested that estradiol acts before, not during, extinction and that its effect on extinction is associated with its illness-inducing properties. This hypothesis is based on previous work which shows an attenuation of conditioned taste aversion learning when rats are exposed to illness-inducing agents during a period that starts 2 days after acquisition and ends 2 days before extinction trials are initiated. Four experiments were designed to test elements of this hypothesis. The first two experiments demonstrated that if an estradiol-filled Silastic capsule is implanted before extinction of a LiCl-induced aversion, when the conditioned taste is not present, it accelerates extinction, but if it is implanted during extinction, when the conditioned taste is present, it prolongs extinction. The third experiment showed that the same dose of estradiol that accelerates extinction of a LiCl-induced aversion was effective in producing a conditioned taste aversion when it was present for 18 h after consumption of a novel sucrose solution. The fourth experiment indicated that serum levels of estradiol were elevated during the 18 h. These results are consistent with the hypothesis that the acceleration of extinction by estradiol is associated with its illness-inducing properties. It is suggested that estradiol acts on neural areas that mediate illness information and that one of these areas, the area postrema is necessary for estradiol to accelerate extinction of a LiCl-induced aversion.     

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.     

Formation of taste aversions in the rat

The presence of correlation between the initial attitude of animals to a certain taste agent and the intensity of conditioned taste aversion (CTA) after LiCl poisoning was studied in nonlineal male white rats. 4 types of behavioural reactions were revealed: 1) the nonspecific inhibitory reaction to the situation in which CTA was elaborated; 2) specific associative-adaptive connection of CTA with the taste agent used (0,1% saccharine solution); 3) complex reaction consisting of the two first ones; 4) the same drinking behaviour as that before CTA elaboration. Moreover, a correlation was found between the initial attitude of animals to certain taste agent and the intensity of CTA after pairing of this agent with subsequent poisoning.     

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.     

Epinephrine-induced conditioned taste aversion

The ability of the hormone epinephrine to induce a conditioned taste aversion was investigated in three experiments. Aversions induced by epinephrine appear more easily conditioned to a highly preferred sucrose solution than to a less preferred sucrose/saline solution. A dose-response curve also exists; better conditioning is evident following injection of either 0.3 or 0.5 mg/kg epinephrine than it is following a 0.1 mg/kg dose. A arcadian rhythmicity also occurs for epinephrine-induced sucrose aversions. When the endogenous levels of this hormone are at trough, conditioning is greater than when they are elevated. This circadian pattern is interpreted with respect to the degree of discriminability between endogenous and exogenous epinephrine levels.     

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.     

Parallel reinforcement pathways for conditioned food aversions in the honeybee

Avoiding toxins in food is as important as obtaining nutrition. Conditioned food aversions have been studied in animals as diverse as nematodes and humans [1, 2], but the neural signaling mechanisms underlying this form of learning have been difficult to pinpoint. Honeybees quickly learn to associate floral cues with food [3], a trait that makes them an excellent model organism for studying the neural mechanisms of learning and memory. Here we show that honeybees not only detect toxins but can also learn to associate odors with both the taste of toxins and the postingestive consequences of consuming them. We found that two distinct monoaminergic pathways mediate learned food aversions in the honeybee. As for other insect species conditioned with salt or electric shock reinforcers [4-7], learned avoidances of odors paired with bad-tasting toxins are mediated by dopamine. Our experiments are the first to identify a second, postingestive pathway for learned olfactory aversions that involves serotonin. This second pathway may represent an ancient mechanism for food aversion learning conserved across animal lineages.     

Some critical factors involved in formation of conditioned taste aversion to sodium chloride in rats

Some factors concerning acquisition and retention of conditionedtaste aversions (CTAs) were behaviorally examined in the rat.In the CTA paradigm, aqueous solution of 0.1 M NaCl was usedas the conditioned stimulus (CS) and an intraperitoneal (i.p.)injection of 0.15 M LiCl was employed as the unconditioned stimulus(US). In experiment 1, CTAs to 0.1 M NaCl were examined in bothforward (CS–US) and backward (US–CS) conditioningparadigms. Reliable CTAs were produced in the US–CS conditioningparadigm when the US–CS interval was less than 10 min,as well as in the CS–US conditioning paradigm. In experiment2, strong CTAs to 0.1 M NaCl were established when water-deprivedrats made at least 500 continuous licks, corresponding to 2.5ml intake and 2 min of drinking time. In experiment 3, effectsof gustatory deafferentation on CTA formation were studied.Only the chorda tympani played an important role in acquisitionand retention of CTAs to NaCl solutions. These results ipHimMthat strong CTAs can be acquired to 0.1 M NaCl, if its tasteinformation which is conveyed via the chorda tympani duringthe 500 continuous licks is followed by LiCl-induced sickness.     

Stimulus specificity in the acquisition and extinction of conditioned taste aversion

An experiment evaluated whether the acquisition and extinction of conditioned taste aversion in the rat is stimulus-specific by testing the degree of response transfer between sweet and salty tastes. Animals in the paired-same and paired-different groups received a presentation of a gustatory CS and a cyclophosphamide injection US. Nonconditioned control groups received unpaired CS /US presentations or the CS followed by a vehicle injection. Taste avoidance was evaluated in three nonreinforced test sessions. In the paired-same, unpaired and vehicle groups, all test sessions were conducted with the same flavor as originally used in training, whereas the paired-different group was tested with a novel flavor on the first and second sessions and with the originally trained flavor in last session. Stimulus specific acquisition was apparent in the first test session, when the animals in the group paired-same exhibited lower fluid intake than the other three groups. Evidence of specificity of extinction was apparent in the last test session, when animals in the group paired-different exhibited lower fluid intake than the other three groups. These results provide further evidence of stimulus specificity in acquisition and extinction of conditioned taste aversion, supporting the associative interpretation of these phenomena.     

The capability of several toxic plants to condition taste aversions in sheep

Grazing livestock frequently ingest toxic plants, occasionally with fatal results. Behavioral adjustments by livestock may reduce toxin intake; for example they can develop food aversions which may protect animals from over-ingestion of toxic plants. The purpose of this study was to evaluate three plants with different mechanisms of toxicity for their efficacy in conditioning a taste aversion: (1) a seleniferous plant, Xylorhiza glabriuscula, (2) an indolizidine alkaloid-containing plant, Astragalus lentiginosus, and (3) a diterpene acid-containing plant, Gutierrezia sarothrae. For each plant species, 15 sheep were divided into 3 treatment groups and periodically tested for consumption of a novel food, whole corn: (1) controls – given 200 g of ground alfalfa hay by oral gavage, (2) averted – given lithium chloride (LiCl) at 175 mg/kg BW via oral gavage, and (3) given the specific target plant by oral gavage. X. glabriuscula was given at a dose equivalent to 3 mg Se/kg BW; A. lentiginosus was given at a dose equivalent to 3 mg/kg of the toxic alkaloid, swainsonine; freshly thawed G. sarothrae was dosed at 5 g/kg body weight (BW). Both LiCl and Xylorhiza conditioned an aversion to corn, with sheep eating 1.6 and 0.6% of offered corn during the final test; controls were not averted, eating 93% of the corn (P < 0.01). Sheep were partially averted by Xylorhiza after a single dose, and the aversion was complete after the second dose. Sheep were not averted by A. lentiginosus or G. sarothrae. Of the three toxic plants used in this study, only Xylorhiza conditioned a taste aversion. These results likely reflect differing mechanisms of action of the plant toxin(s) on brain and gut structures important for forming conditioned taste aversions. These results suggest that conditioned aversions to Se-containing plants may help to deter consumption of such plants by grazing ruminants on rangelands.     

Genetic differences in nicotine-induced conditioned taste aversion

Genetic differences in nicotine-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J, DBA/2J, BALB/cJ and C3H/heJ mice were adapted to a 2-h per day water access regimen. Subsequently, mice received nicotine injections (0.5, 1.0 or 2.0 mg/kg) immediately after 1-h access to a NaCl flavored solution. DBA and C3H mice developed dosedependent aversions to the nicotine-paired flavor. BALB mice showed only minor reductions in intake with no difference between the nicotine dose groups. C57BL mice did not show development of nicotine-induced conditioned taste aversion. These results demonstrate that nicotine's aversive motivational effect is strongly influenced by genotype. Further, genetic sensitivity (DBA mice) or insensitivity (C57BL mice) to nicotine-induced conditioned taste aversion was similar to reports of genetic sensitivity to ethanol's aversive effect measured in this design.     

Generalization of learned taste aversions in rabbits: similarities among gustatory stimuli

Although rabbits have been used in a number of electrophysiologicaland anatomical studies on the gustatory system, there have beenfew behavioral experiments on these animals and these have beenlimited to studies of taste preference. The similarities amonga number of gustatory stimuli were assessed in rabbits by measuringthe generalization patterns in a conditioned taste aversionexperiment. Rabbits were trained to take their daily rationof water within a 30-min session, during which the number oflicks per 10-s presentation of a drinking tube could be recorded.During one of these sessions, one of 12 stimuli (sucrose, fructose,Na-saccharin, NaCI, NaNO₃, Na₂SO₄, KC1, NH₄C1, CaCl₂, HC1, QHC1or urea) was presented, followed by i.p. injection of LiCl toproduce a conditioned taste aversion. Animals were then testedwith all of the stimuli and the amount of suppression of lickingwas used as a measure of stimulus generalization. The patternsof generalization were compared for the test and conditioningstimuli separately. Some nonreciprocities were seen betweenthe conditioning and test stimuli, which reflected the occurrenceof multiple taste qualities and the tendency for aversions togeneralize more to stronger stimuli than to weaker ones. Principalcomponents analysis of the stimulus relationships showed thatrabbits responded to these stimuli in a fashion similar to thatof other mammals, including humans. Within the principal componentssolution, there were strong similarities among the sugars, thesodium salts, the nonsodium salts and the bitter-tasting stimuli.     

Generalization of conditioned food aversions in grazing sheep and its implications for food categorization

When grazing on heterogeneous pastures, herbivores may rely on food item generalization and categorization processes for reducing information processing while selecting their diet. The objective of this study was to assess the generalization of an aversion by grazing sheep for items differing by one or two criteria from an item against which they were negatively conditioned. Four items cultivated in pots were offered to the animals, resulting from the combination of an intrinsic criterion, i.e. grass species (ryegrass and fescue) and a transitory criterion, i.e. sward height (tall and short). We assessed the generalization process by comparing binary choices between the initially preferred tall ryegrass and the three other items, before and after animals had been partially conditioned against tall ryegrass. This method proved useful in assessing the generalization of an aversion. Sheep did not generalize their aversion on the basis of sward height but rather on species: they increased their preference for tall fescue and decreased their instantaneous preference for short ryegrass after having been conditioned against tall ryegrass. The generalization of an aversion through different states of a same species could indicate the possibility of a species-based categorization by grazing herbivores.     

An exception to the rule: common vampire bats do not learn taste aversions

Conditioned taste aversions function by preventing an organism from ingesting a food previously associated with gastrointestinal malaise. Taste-aversion learning has been observed in many animals: molluscs to mammals, insects to birds. However, among mammals, neither bats nor monophagous species have been investigated adequately. Here we show that although three dietary generalists (one insectivorous and two frugivorous bats) readily acquired taste aversions, the common vampire bat, Desmodus rotundus, a monophageous feeder on vertebrate blood, did not learn to associate a novel flavour with aversive gastrointestinal events. We interpret these data as consistent with the hypothesis that taste aversions are an adaptive specialization of learning. Copyright 2003 The Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved.