Flavor Aversion Research Articles

The NMDA-Receptor Antagonist Ketamine as an Unconditioned Stimulus in Taste Aversion Learning

Three experiments studied the effectiveness of ketamine acting as an aversive unconditioned stimulus (UCS) in a conditioned flavor aversion procedure. In Experiment 1a, three conditioning trials where sucrose was paired with ketamine produced a weak but significant aversion to sucrose; Experiment 1b showed that this effect was not due to a reduced consumption of sucrose caused by ketamine-induced neophobia. In Experiment 2, acquisition of an aversion to sucrose paired with lithium chloride (LiCl) injections was retarded by prior repeated exposure to LiCl but not to ketamine. These results are not consistent with an interpretation of previous results, showing that ketamine impairs the acquisition of flavor aversions based on LiCl-induced illness, as an example of the UCS preexposure effect.

Effects of a Retention Interval on the US-Preexposure Phenomenon in Flavor Aversion Learning

Two experiments, using rats as subjects, examined the effects of a retention interval on the retardation of flavor aversion learning produced by prior exposure to the unconditioned stimulus (US). Experiment 1 showed that the US-preexposure effect was attenuated when a 15-day retention interval was interposed between preexposure and conditioning, but that the same interval was without effect when it occurred between conditioning and testing. Experiment 2 confirmed these findings and also demonstrated that these retention intervals did not influence the conditioned aversion shown by control subjects not given US preexposure. These results are consistent with the proposal that the US preexposure has its effect by interfering with the formation of the target association; they provide no support for the suggestion that the effect depends on interference at the test stage.

Mild Conditioned Food Aversions Developed by Sheep Towards Flavors Associated with Plant Secondary Compounds

The objectives of the experiment were to test whether sheep develop conditioned flavor aversions (CFAs) towards a food flavor associated with the administration of a plant secondary compound, and providing that such CFAs develop, to determine how long they persist. For experimental purposes, two natural secondary compounds were used—quebracho (mainly condensed tannins) and oxalic acid—at doses previously known to produce negative postingestive consequences in sheep. The experiment consisted of four conditioning periods (each eight days long) during which the novel flavored foods (flavored hay) were offered concurrently with oral administration by gavage of the secondary compounds. In the conditioning period four groups of sheep (N = 6 each) were arranged such that each group received different flavored feeds (orange and aniseed) for two-day sequential periods. One flavor was paired with one of the model secondary compounds. Between the two sets of two days and after the second two-day period there was a period of two “rest” days, to avoid residual physiological effects of secondary compound administration. The intakes of flavored hay were recorded during each conditioning day and the effects of the secondary compounds were quantified in rumen (for volatile fatty acids and ammonia concentrations) and blood samples (for plasma calcium levels). At the end of each conditioning period, the preference for the two flavors was measured by a two-choice short-term preference test (20 min each); the persistence of the CFAs was similarly measured at 0, 10, 30 and 60 days after the completion of the conditioning with two-choice longterm preference tests (3 hr each). Results of the experiment indicated that quebracho administration did not lead to development of CFAs at the level administered. This does not necessarily reflect the sheep's inability to develop CFAs towards tannins but may reflect possible trade-offs between the ingestion of nutrients and secondary compound concentration that might have been imposed on the sheep in this experiment. In other words, it might reflect the increased familiarization with the hay (i.e., increase in its intake and hence of nutrients), which overcame the negative effects of quebracho administration. However, oxalic acid caused CFA in sheep: hay intake tended to be reduced during the days that the secondary compound was administered, and importantly the secondary compound associated flavored hay was partially avoided during the two-choice preference tests. The latter avoidance was not affected by time (consistent across conditioning periods). This CFA persisted for up to 60 days after the completion of conditioning in the absence of intervening oxalic acid exposure. Thus, sheep were able to form CFAs towards a flavor associated with the administration of a naturally occurring organic plant secondary compound.

Effects of Acute and Repeated Exposures to Aroclor 1254 in Adult Rats: Motor Activity and Flavor Aversion Conditioning

Effects of Acute and Repeated Exposures to Aroclor 1254 in Adult Rats: Motor Activity and Flavor Aversion Conditioning

Immunological induction of flavour aversion in mice. II. Passive/adoptive transfer and pharmacological inhibition.

Mice immunized with ovalbumin develop a strong aversion to ingesting sweetened egg white dilutions or ovalbumin solutions. In immunized animals, gavage or voluntary ingestion of ovalbumin triggers an increase of vascular permeability in the intestine; pretreatment with a mixture of histamine and serotonin antagonists blocked this reaction, but not the aversion; dexamethasone inhibited both the aversion and the increase in permeability. The aversion was transferred to normal recipient mice with high-titre anti-Ova sera obtained with complete Freund's adjuvant, but not with lower-titre serum pools of mice immunized with the help of Al(OH)3 adjuvant. However, the aversion was also (adoptively) transferred with whole spleen cells from immune donors. This later condition is inefficient to transfer the formation of high titres of specific antibodies.

Stimulus specificity in flavor acceptance learning

Infusing rats with 6% carbohydrate whenever they drank a test fluid stimulated their intake of 0.03–0.3% saccharin, 0.9% sodium chloride, and 0.5% oligosaccharide solutions within 1 to 3 days, but did not greatly increase intake of cherry-flavored water, 2% saccharin, 0.45% sodium chloride, monosodium glutamate, 0.025% sucrose octaacetate, or 0.4% maltodextrin, when food was available ad lib. In general, it was more difficult to detect an effect with aversive stimuli, but it was possible to detect a significant effect with one such aversive flavor by either increasing the number of animals to permit detection of a small effect, or by using a preference test. For most stimuli, however, rats that had been trained with food available and then tested when food deprived showed significant increases in fluid intake, compared to rats that had been given the same flavor without carbohydrate infusions, even when plain water was infused in all rats during the food deprivation test. The following forms of evidence indicate that the increased intake is due to a form of Pavlovian conditioning. It tends to increase over repeated trials and to persist for a day after the carbohydrate infusions have been discontinued. Indeed, in one experiment, increased intake even persisted for a day when the infusion conditions were reversed, such that control rats were infused with carbohydrate and experimental rats were infused with water. Increased ingestion is attenuated by preexposure to the infusion in the absence of an appropriate taste solution. Increased ingestion is attenuated by preexposure to the taste solution in the absence of infusions (i.e., latent inhibition). Although increased intake is a form of associative conditioning, it is unlike malaise-conditioned taste aversions because taste aversions were conditioned to monosodium glutamate, cherry flavor, and saccharin with equal ease. The ease with which infusion increased intake is influenced by at least three different factors, degree of aversiveness, stimulus intensity, and rats' innate predisposition to acquire certain stimulus-response relationships more readily than others.

Changes in the Expression of Stimulus Selection: Blocking Represents Selective Memory Retrieval Rather Than Selective Associations

Initial studies reporting changes in the expression of stimulus selection as a function of the length of the interval between training and testing have been restricted to the conditioned taste aversion procedure. The present study examined the influence of the length of retention interval on the stimulus selection phenomenon of blocking when external cues were used as conditioned stimuli and suppression of activity served as the measure of conditioning. Similar to findings in flavor aversion conditioning, the expression of blocking was dependent on the length of the interval between training and testing. The results indicate that blocking, like overshadowing, does not necessarily represent a failure in acquisition, but rather suggest an explanation of certain instances of blocking in terms of changes in the relative retrievability of learned associations over time.

LSD produces place preference and flavor avoidance but does not produce flavor aversion in rats.

LSD produces place preference and flavor avoidance but does not produce flavor aversion in rats.

No Evidence for Modulation of Evaluative Flavor–Flavor Associations in Humans

In four experiments using a human evaluative flavor–flavor association paradigm, we investigated whether the acquisition of stimulus valence may be subject to Pavlovian modulation or occasion setting. In all studies, subjects (Ss) were exposed to a feature-positive (FP) (XA+/A−) schedule (or a modified version of it), in which flavor A was reinforced by the aversive flavor Tween 20 if and only if it was accompanied by a feature stimulus X. It was expected that Ss would develop an X-dependent dislike for A. In Experiment 1, for half of the Ss a quasi-sequential FP schedule was used, whereby the color of the liquids functioned as X. The other half of the Ss were exposed to a positive-patterning (PP) (XA+/A−/X−) schedule, in which unreinforced color (X−) trials were added to the FP schedule. Both schedules resulted in an unmodulated dislike for flavor A. In Experiment 2, Ss were exposed to a modified FP schedule, in which flavor A was reinforced by Tween 20 when presented with color X, while A was reinforced with positive sugar when presented colorless. Ss again demonstrated an unmodulated dislike for A. Experiment 3, using a sequential FP (X → A+/A−) schedule in which a flavor functioned as X, also resulted in an unmodulated dislike for A. Finally, in Experiment 4, Ss were exposed to the modified FP schedule, in which flavor A was presented with Tween 20 when preceded by flavor X, while A was reinforced with Sugar when not preceded by X. For those Ss liking sugar, no valence shifts were observed, whereas for those not liking sugar, the standard unmodified dislike for A was obtained. Some suggestions are provided with respect to variables which might be related to the absence of modulation.

Analysis of polysaccharide taste in hamsters: Behavioral and neural studies

A series of studies was carried out in hamsters ( Mesocricetus auratus) to determine whether polysaccharides have behavioral and neurophysiological characteristics that distinguish them from simple sugars. Behavioral studies utilized solutions of glucose, maltose, sucrose, Polycose, and glycogen in two-bottle preference tests and in tests of generalization of conditioned taste aversions. Multiunit and single-unit responses of the chorda tympani nerve were studied with the same stimuli. Neural responses to Polycose and glycogen were found to be generated primarily by ionic contaminants. Dialysis or deionization dramatically reduced electrophysiological responses, a result consistent with occurrence of Polycose and glycogen sensitivity in electrolyte-sensitive nerve fibers. Effects of treatment with the Na +-channel blocker amiloride and cross-adaptation were also consistent with neural responses generated by ionic contaminants. Hamsters showed strong preferences for the sugars and Polycose, a mixture of glucose polymers with α-1,4 linkages, and even stronger preferences for a glycogen preparation. Conditioned flavor aversions were established to glycogen, sucrose, and maltose, but no aversion was learned to 3.2% Polycose. The learned aversion to maltose partly generalized to glycogen and sucrose, but sucrose and glycogen did not cross-generalize. Deionization did not affect the preferences for Polycose and glycogen but removal of contaminants of mol.wt ≤ 7000 Da greatly reduced preference for glycogen. In conclusion, glycogen itself, after removal of low molecular weight contaminants, is a poor taste stimulus in hamsters, both behaviorally and neurophysiologically. However, Polycose is highly preferred by hamsters but gives little chorda tympani response after removal of ionic contaminants. In alert animals, the action of salivary amylase on polysaccharides may produce simpler, detectable taste stimuli.

LSD produces place preference and flavor avoidance but does not produce flavor aversion in rats.

The hedonic properties of lysergic acid diethylamide (LSD) were assessed using the place conditioning, taste reactivity, and taste avoidance tests. LSD produced a conditioned place preference, but only at the highest dose tested (0.2 mg/kg). A single preexposure to the conditioning chamber (latent inhibition) prevented the establishment of a place preference. When paired with sucrose, doses of 0.05 to 0.2 mg/kg of LSD produced taste avoidance, but no dose of LSD produced an aversion to the taste as assessed by the taste reactivity test. These results suggest that LSD, like other rewarding drugs, produces taste avoidance by a mechanism other than that produced by emetic drugs.

2335 A neural substrate for taste-illness association in taste aversion learning in rats

In two experiments rats with subdiaphragmatic vagotomies were compared to sham-operated rats in the acquisition and extinction of a flavor aversion with ethanol as the illness-inducing agent. Vagotomized rats developed aversions equivalent to those of sham-operated rats whether the ethanol was administered intragastrically (Experiment 1) or intraperitoneally (Experiment 2). Because vagotomy eliminates the majority of sensory input from the gastrointestinal tract, ethanol must exert its aversive effects as a blood-borne toxin rather than as a gastrointestinal irritant.

Perceptual learning in flavor aversion conditioning: Roles of stimulus comparison and latent inhibition of common stimulus elements

In three experiments, rats received training in which an aversion was established to one flavor and the extent to which this aversion generalized to a second flavor was tested. Experiment 1 showed that nonreinforced preexposure to both flavors resulted in reduced generalization between them. Experiments 2 and 3 demonstrated that this reduction in generalization required the two flavors to be presented on alternate trials during preexposure. Subjects given preexposure consisting of a block of trials with one flavor followed by a block of trials with the other showed the same degree of generalization as subjects given no preexposure. The two schedules of stimulus presentation were equated in the total amount of exposure given to each stimulus, making it unlikely that differences in latent inhibition could be responsible for the difference seen on the test. It is suggested that the opportunity for stimulus comparison offered by the alternating schedule might be important in a process of perceptual learning that is responsible for the reduced generalization.

Effects of the NMDA receptor antagonist ketamine on flavor memory: Conditioned aversion, latent inhibition, and habituation of neophobia

In four experiments with rats, the effects of the NMDA antagonist ketamine on several forms of gustatory learning were studied. Replicating previous findings, in Experiment 1 ketamine was shown to impair one-trial acquisition of a flavor aversion at the dose of 25 mg/kg, but also produced a significant state-dependency effect. In Experiment 2 ketamine did not alter the process of habituation of neophobia to a new flavor. Abolition of latent inhibition by ketamine injected before preexposure in Experiment 3a was not replicated in Experiment 3b when ketamine was injected before all phases of the experiment. Finally, in Experiment 4 rats injected with ketamine showed slower acquisition of a flavor aversion with a multiple-trial procedure but finally reached a level similar to that shown by saline controls. The implications of these results for an interpretation of the effects of ketamine on flavor aversion learning in terms of interference with flavor memory storage are discussed.

Mimetic behavior of rats in flavor aversion learning

Rats exposed to odor (almond), taste (saccharin) or an odor/taste-compound (almond/ saccharin) in a one-trial conditioning were subsequently poisoned with lithium chloride either 5 min (Ex) or 16 h (Co) after drinking. We measured various behavioral CRs elicited by these conditioned stimuli. All stimuli and compounds produced strong flavor aversions and elicited a pattern of agitated behavior characterized by increased general activity, rearing, and the specific mimetic response ‘gaping’ in the experimental groups. No comparable patterns were observed in the control groups. In the compound-experimental group an overshadowing effect for the odor component by the new taste was found. However, odor in this condition still elicited somewhat reduced drinking and the typical aversive reaction pattern. Behaviors induced by pairing odor with illness were more strongly controlled by the presence of the poisoned odor in the compound condition than in the odor condition. The compound experimental group discriminated more strongly, in general, behaviors and in their mimetic responses between the time when odor was presented or not in a test procedure, which alternated poisoned odor and air.

Glucose polymer taste is not unitary for rats

Rats have an acute sense of taste for maltodextrins, substances which are sometimes called glucose polymers, polysaccharides, or Polycose ®. The present studies examined rats' responses to two maltodextrin preparations. One maltodextrin, a maltooligosaccharide, had an average chain length of 4.4 glucose units. The other maltodextrin was a maltopolysaccharide, having an average chain length of 22. In 24-h preference tests, rats strongly preferred 1% and 5% maltodextrin over water, regardless of the type of maltodextrin offered. When given a choice of two maltodextrins, rats preferred the maltooligosaccharide, but the degree of preference was influenced by the rats' previous experience with maltodextrins. Conditioned flavor aversion experiments were conducted to determine whether rats detect qualitative flavor differences between the these two maltodextrins. Rats trained to avoid one maltodextrin also avoided the other maltodextrin. Nevertheless, rats could be trained to drink maltooligosaccharide but avoid maltopolysaccharide; these rats showed no reliable tendency to respond to the intensity of maltooligosaccharide flavor. Therefore, maltodextrins of varying chain length differ more in flavor quality than in flavor intensity. This difference in flavor quality is not attributable to known sweet and starch flavors because neither maltodextrin contained much glucose and because rats trained to avoid the polysaccharide did not avoid starch. Because rats can discriminate between solutions containing only 0.5–1% maltodextrin, their ability to discriminate among carbohydrates must be far more acute than that of humans.

The effect of flavor concentration and toxin dose on the formation and generalization of flavor aversions in lambs.

If an animal experiences gastrointestinal malaise after eating a novel feed, it develops a dislike for the feed called a conditioned flavor aversion (CFA). Understanding flavor aversions is important for diet-training procedures, understanding animal responses to poisonous plants, and preparing animals for new foraging environments. Our research objectives were to determine how variation in 1) flavor concentration (oregano) and 2) dose of gastrointestinal toxin (lithium chloride; LiCl) affected the establishment of CFA in lambs. In a series of experiments feeding lambs ground grains mixed with oregano, we examined how the formation of a CFA to one ground grain, with or without oregano, influenced the consumption of another oregano-flavored grain. We determined that 1) the higher the toxin dose, the stronger the CFA, the greater the generalization of the CFA to a similar feed, and the greater the avoidance of a novel feed; 2) lambs generalized aversions from familiar to novel feeds when both feeds had a flavor in common; and 3) the concentration or intensity of feed flavor apparently did not affect the acquisition or generalization of a CFA, but it did influence the acceptance of a novel feed. Our findings suggest that flavor aversions may be important in the acceptance of harvested or processed feeds.

Ruminal metabolism of leafy spurge in sheep and goats: A potential explanation for differential foraging on spurge by sheep, goats, and cattle

Leafy spurge (Euphorbia esula) is an introduced forb that is invading western rangelands. Goats (Capra hircus) readily graze the plant, but cattle (Bos tarus) generally and sheep (Ovis aries) locally appear to develop conditioned flavor aversions to leafy spurge. They either avoid the plant entirely or graze it reluctantly. We hypothesized that: (1) a diterpene diester that can occur in leafy spurge was an aversive agent, and (2) diet selection differences among ruminant species may be partly a function of differential ruminai metabolism of aversive phytochemicals, and further that cattle and sheep may be reluctant to graze leafy spurge because their ruminai microbes do not metabolize certain leafy spurge chemicals as do ruminai microbes in goats. Sheep did not develop an aversion to a novel food when its consumption was followed by an intravenous injection of ingenol 3,20-dibenzoate (P=0.34). Sheep did develop an aversion to a novel food when its intake was followed by a dose of leafy spurge fermented with sheep ruminai digesta, but not when followed by a dose of leafy spurge fermented with goat ruminai digesta (P= 0.03). This suggests that goat ruminai microbes may modify leafy spurge such that it does not elicit an aversion in sheep.

Cattle Avoidance of Leafy Spurge: A Case of Conditioned Aversion

Leafy spurge (Euphorbia esula L.) represents a serious threat to the productivity and profitability of many cattle ranches in the midwestern U.S. Sheep and goats will graze the weed, but cattle generally do not. We hypothesized that cattle avoid leafy spurge because it contains 1 or more chemicals that elicit a conditioned flavor aversion when consumed. First, we tested cattle to determine if they reduced their intake of a novel feed on subsequent days if we modestly increased rumen fill by introducing additional feed or additional feed plus an aversive agent (lithium chloride, LiCl) after they had consumed the novel feed. We observed that cattle became averted (P = .0001) to the novel feed only when LiCl was administered with additional feed. Simply increasing rumen fill by a small amount did not cause cattle to reduce their intake of the novel feed the following day. Secondly, we tested cattle to determine if they reduced their intake of a novel feed on subsequent days if we introduced leafy spurge into their rumina following consumption of the novel feed. We also tested cattle to determine if a spurge-induced aversion to a novel feed was preventable by inoculation with rumen microbes from sheep with spurge in their diets. We found that introducing spurge into cattle after their intake of novel feed reduced (P .40) aversions to a novel feed paired with spurge introductions. Apparently, cattle avoid leafy spurge partly or wholly because they develop a conditioned aversion after first ingesting some threshold amount of it.

How herbivores track variable environments: Response to variability of phytotoxins

The concentration of toxins in plants can vary with plant phenology and environmental factors. Changes in toxicity may or may not be associated with changes in plant flavor. These factors may make it difficult for herbivores to avoid toxic plants. We conducted three experiments concerning animals' ability to detect toxins. In experiment 1, we examined whether animals familiar with a tastable toxin on food would adjust intake when toxin concentrations changed. Lambs were initially offered oats with either a low, medium, or high concentration of lithium chloride (LiCl; a salty-tasting toxin). Later, when all lambs were offered oats with the medium concentration of LiCl, lambs that were conditioned with the low LiCl concentration decreased intake while lambs conditioned with the high LiCl concentration increased intake. In experiment 2, we examined flavor aversions formed when animals sampled food with two flavor levels prior to illness. Lambs initially ate the same amount of barley with a low and with a high concentration of either sodium saccharin (a sweet flavor) or aluminum sulfate (a bitter flavor). Lambs then received a mild dose of LiCl. Later, when lambs were offered a choice between barley with either a low or high flavor concentration, lambs preferred the barley with the low flavor concentration. Experiment 3 examined how variable toxicity affected intake when the flavor remained constant. Lambs were initially offered oregano-flavored barley and then received a dose of LiCl. Lambs received either a medium dose, a high dose, or a dose that varied randomly among low, medium, or high amounts of LiCl. Lambs in the medium dose group ate more oregano-flavored barley at the end of the trial than did lambs in either of the other groups.