Pica behavior of laboratory rats (Rattus norvegicus domestica): Nauseated animals ingest kaolin, zeolite, bentonite, but not calcium carbonate chalk.

"Pica" refers to the ingestion of non-nutritive substances by animals that would not typically consume them. The pica behavior can be utilized to investigate the internal conditions of animals' bodies. For example, rats, due to neuroanatomical reasons, cannot vomit; nevertheless, when nauseated, they ingest kaolin clay. This renders the ingestion of kaolin a practical proxy for measuring nausea in rats. The question of whether rats consume minerals other than kaolin during nauseous episodes remains unanswered. This study aims to identify a mineral better suited for detecting nausea in rats. In two experiments, nausea was induced in laboratory rats by a single dose of lithium chloride (0.15 M, 2% bw), and their mineral consumption over the 24-hour period was measured. Experiment 1 compared three minerals between rat groups: kaolin sold for nausea detection (kaolin A), kaolin for ceramics (kaolin B), and zeolite. Nauseated rats consumed all minerals, with the highest consumption occurring with kaolin B. In Experiment 2, three commercially available health soils were compared: edible kaolin, edible bentonite, and edible chalk. The most significant consumption was observed in the kaolin group, followed by the bentonite group, while nauseated rats did not consume edible chalk. These findings underscore the suitability of kaolin for nausea detection, although the extent of consumption may vary depending on the product.

Preexposure to running attenuates rats' running-based flavour avoidance: Testing associative blocking with a cover cues or context change.

Voluntary running in activity wheels by rats leads to a Pavlovian conditioned aversion to the flavour consumed immediately before the running, causing the rats to avoid that flavour. This learning process, known as running-based flavour avoidance learning (FAL), is weakened when the rats have had repeated exposure to the wheels before. According to the associative account, the association between the background context and running established during the preexposure phase blocks the conditioning of the target flavour because the running is highly predictable by the background context from the outset of the FAL phase. Experiments 1 and 2 examined this account by introducing another flavour as a cue signalling wheel access during the preexposure phase. In the framework of the associative account, the introduction of this cue should impede the formation of the context-running association during the preexposure phase, thereby hindering the contextual blocking of aversive conditioning for the target flavour in the FAL phase. This would result in unweakened FAL. Although the results of Experiment 1 align with this prediction, in Experiment 2, when highly distinct flavours were used as the target and second cues, the preexposure effect was not eliminated. This contradicts the predictions of the associative account, indicating that Experiment 1 may have been influenced by stimulus generalisation. In Experiment 3, changing background contexts between the preexposure and FAL phases had no impact on the preexposure effect, contrary to the predictions of the associative account. In general, the associative account was not supported.

Food avoidance learning based on swimming in laboratory mice (Mus musculus).

Although it is now well documented that laboratory rats learn to avoid the flavored substance consumed immediately before running in activity wheels or swimming in water buckets, research on this activity-based flavor avoidance learning in other species is limited. Recently, running-based flavor avoidance learning has been demonstrated in laboratory mice by employing a method of resistance-to-habituation of neophobic reaction to novel food; mice that repeatedly experience running after encountering a novel food have a prolonged tendency to reject that food compared to control mice without paired running. The present article reports a series of attempts to obtain evidence of flavor avoidance learning based on swimming rather than running using this resistance-to-habituation method. Swimming-based flavor avoidance was clearly demonstrated in a differential conditioning paradigm; however, its demonstration in a simple conditioning paradigm requires a post-training choice test of the target food and another type of food. These results are likely due to the short swimming time (20 min) and the formation of weak flavor aversion.

Pica caused by emetic drugs in laboratory rats with kaolin, gypsum, and lime as test substances.

Pica refers to eating nonfood substances. The pica behavior has been the focus of attention in physiological and pharmacological studies, because its consumption is a good marker of nausea in laboratory rats, which cannot vomit due to neuroanatomical reasons. Almost all pica studies with rats have used kaolin clay pellets as nonfood substances. The present study primarily aimed to explore an alternative (or more suitable) substance to kaolin for detection of nausea induced by emetic drugs. Two calcium compounds, gypsum and lime, were evaluated in this study. An injection of lithium chloride (LiCl) increased pica behavior not only in the rats given kaolin but also in the rats given gypsum, suggesting that gypsum consumption could be used as an indicator of nausea. However, its sensitivity was no greater than that of kaolin consumption. In addition, lime is not a useful marker for nausea because the size of pica was small in the LiCl-injected rats, and did not differ from the control in the cisplatin-injected rats. In short, the superiority of kaolin as a test substance for nausea could not be overturned. However, the fact that nauseous rats displayed pica behavior with gypsum and lime refutes the claim that aluminosilicate, the main component of kaolin, is the critical determinant of emetic-caused pica in laboratory rats.

Food avoidance learning based on entirely voluntary wheel running in laboratory mice (Mus musculus).

Previous studies (Nakajima, 2019a,b) demonstrated food avoidance learning based on wheel running in laboratory mice: Consumption of a target snack becomes suppressed if it is repeatedly paired with an opportunity to run in an activity wheel. This is a kind of Pavlovian conditioning, because the avoidance is specific to the paired snack. For example, in an experiment, mice were initially trained to run in closed wheels. Then, access to one of the two kinds of snacks (cheese or raisins, counterbalanced) was followed by confinement in a large pet cage with an open wheel, while access to the other snack was not. After several repetitions of these two types of trials, differentiation in consumption between the two snacks emerged: The intake of the unpaired snack increased gradually over days, while the increase was attenuated for the running-paired snack. The present study replicated this food avoidance learning without the pretraining of running in a closed wheel, emphasizing the intrinsic capacity of running to establish food avoidance. The results somewhat suggest that pretraining in open wheels facilitates running-based food avoidance, but this effect was too weak in the present study to draw a clear conclusion.

Effect of pretrial running on running-based taste aversion learning in rats.

Voluntary wheel running works as an effective unconditioned stimulus (US) to establish conditioned taste aversion (CTA) in rats with a preceding taste solution as a conditioned stimulus (CS): repeated CS-US pairings evoke avoidance of the CS in the two-choice (CS vs. tap water) test administered at the end of the training. Experiment 1 demonstrated that exposure to running immediately before each CS-US trial alleviates CTA. Subsequent two experiments explored the characteristics of the proximal US-preexposure effect: the alleviation of CTA by the pretrial running was not affected by changing the background contexts between the pretrial and the trial running (Experiment 2) or by signaling the pretrial running via another taste cue (Experiment 3). These results indicate the robustness of the proximal US-preexposure effect and fit well with the predictions of Wagner's (1976, 1978) priming theory. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Further demonstration of running-based food avoidance learning in laboratory mice (Mus musculus).

Voluntary wheel running has hedonically bivalent properties in laboratory rats and mice. While it works as a reward for instrumental performance such as bar pressing, it also functions as an aversive stimulus to establish Pavlovian conditioned avoidance of the paired stimulus. The present study focused on the latter case. Running in closed wheels hampered habituation of a reluctance to eat a target snack in rats (Experiment 1A) and mice (Experiment 1B) trained by pairing access to a target snack with confinement to a wheel attached to the cage. Experiment 2 successfully confirmed and extended this finding with mice running in both open and closed wheels. A differential conditioning procedure employed in Experiment 3 ensured that this phenomenon is specific to the snack paired with running, implying that it reflects Pavlovian conditioned flavor avoidance (CFA). Free exploration in cages without wheels, however, did not results in a CFA.

Food aversion learning based on voluntary running in non-deprived rats: a technique for establishing aversive conditioning with minimized discomfort.

This article presents an experimental preparation for establishing conditioned food aversion (CFA) by voluntary wheel running in rats with laboratory chow and water freely available. In Experiment 1, unfamiliar food (raisins) was avoided by rats when they first encountered it. This neophobic food avoidance was habituated by repeated tests; the rats gradually increased their raisin consumption. However, the consumption remained suppressed in rats that accessed the raisins after wheel running. This finding implies that running yielded CFA, which suppressed consumption of the unfamiliar food rather than increasing it. Because running generated kaolin clay ingestion, which is a behavioral marker of nausea, it is suggested that the running-based CFA was mediated by weak gastrointestinal discomfort. Experiment 2 supported the claim that the suppressed consumption is due to running-based CFA by showing the specificity of food suppression. Demonstration of CFA based on voluntary activity in non-deprived rats will contribute to basic research on learning and memory as an alternative technique for studying aversive conditioning with minimized discomfort in animals.

Food avoidance learning based on voluntary wheel running in laboratory mice (Mus musculus).

Mice show a reluctance to eat unfamiliar food, when they first encounter it. This neophobic reaction is conventionally habituated by repeated trials: the mice gradually increase their consumption of the novel food. The new finding reported here is that the consumption remains low in mice that voluntarily run in activity wheels after the novel food access. This effect implies that running yields Pavlovian conditioned flavor aversion, which suppresses, otherwise increasing, consumption of the novel food. In the present research, the effect was demonstrated with a between-group design by pitting experimental mice receiving cheese-running paired treatment against cheese/running unpaired control mice (Experiment 1). The running-based food avoidance in mice was also shown in a differential conditioning paradigm, where one of two novel snacks (chocolate and marshmallow) was paired with running while the other was not, in non-deprived animals (Experiment 2 A) and food-deprived animals (Experiment 2B). These results concord with those previously reported in rats, indicating the generality of the phenomenon.

Clay eating attenuates lithium-based taste aversion learning in rats: A remedial effect of kaolin on nausea.

Kaolin clay eating has been considered as a marker of nausea in rats, because a variety of treatments, which evoke nausea in humans, generate consumption of kaolin clay in rats. The present study with two experiments replicated kaolin clay ingestion induced by an injection of emetic lithium chloride (LiCl). The LiCl injection, however, did not generate eating of wooden objects in rats. The present study also provides a new finding that consumption of kaolin clay alleviates rats' taste aversion learning caused by an LiCl injection. This finding is congruent with the contention that consumption of kaolin clay is not only a useful index of, but also an effective remedy for, drug-induced nausea in rats.

Running-based pica and taste avoidance in rats.

Running in an activity wheel generates pica behavior (kaolin clay intake) in rats. Wheel running also results in Pavlovian conditioned avoidance of the taste solution consumed immediately before the running. Since pica has been considered a behavioral marker of nausea in rats, these findings suggest that wheel running induces nausea, which is the underlying physiological state for establishing taste avoidance. This article reports a replication of running-based pica in rats (Experiment 1) and concurrent demonstrations of running-based pica and taste avoidance in the same animals (Experiments 2 and 3). Also shown is that pica does not alleviate running-based taste avoidance (Experiment 3). Another finding is that pica is generated by a nausea-inducing lithium chloride injection but not by a pain-inducing hypertonic saline injection (Experiment 4). These results, when taken together, support the hypothesis that pica behavior generated by wheel running reflects nausea in rats.

Swimming-based pica in rats.

We have recently demonstrated that voluntary or forced running in activity wheels yields pica behavior (kaolin clay intake) in rats (Nakajima, 2016; Nakajima and Katayama, 2014). The present study provides experimental evidence that a single 40-min session of swimming in water also generates pica in rats, while showering rats with water does not produce such behavior. Because kaolin intake has been regarded as a measure of nausea in rats, this finding suggests that swimming activity, as well as voluntary or forced running, induces nausea in rats.

Running induces nausea in rats: Kaolin intake generated by voluntary and forced wheel running.

Three experiments were conducted showing rats' pica behavior (kaolin clay intake) due to running in activity wheels. The amount of kaolin consumed was a positive function of the available time of voluntary running (20, 40, or 60 min), although this relationship was blunted by a descending (i.e., 60 â†’ 40 â†’ 20 min) test series of execution (Experiment 1). Pica was also generated by forced running in a motorized wheel for 60 min as a positive function of the speed of wheel rotations at 98, 185, or 365 m/h, independent of the order of execution (Experiment 2). Voluntary running generated more pica than did forced running at 80 m/h, although the distance travelled in the former condition was 27% lesser than that in the latter condition (Experiment 3). Because kaolin intake is regarded as a reliable measure of nausea in rats, these results show that wheel running, either voluntary or forced, induces nausea in rats.

Running-based pica in rats. Evidence for the gastrointestinal discomfort hypothesis of running-based taste aversion.

Voluntary running in an activity wheel establishes aversion to paired taste in rats. A proposed mechanism underlying this taste aversion learning is gastrointestinal discomfort caused by running. We tested this hypothesis by measuring the pica behavior (kaolin clay intake) of rats, because it is known that rats engage in pica behavior after various nausea-inducing treatments including irradiation, motion sickness, and injection of emetic drugs such as lithium chloride (LiCl). Following a demonstration of the already-known phenomenon of LiCl-based pica in Experiment 1, we successfully showed running-based pica behavior in Experiment 2 where the running treatment was compared with a non-running control treatment (i.e., confinement in a locked wheel). These results suggest that not only LiCl but also running induces nausea in rats, supporting the gastrointestinal discomfort hypothesis of running-based taste aversion learning.

[Is superstitious behavior more easily acquired by negative reinforcement schedules than positive reinforcement schedules? Examinations of the polarity and the duration of a consequence].

This study investigated the effects of positive and negative reinforcement on superstitious behaviors. Participants were instructed to produce the word "GOOD" on a computer display (positive reinforcement condition) or to remove the word "BAD" (negative reinforcement condition) by pressing any of six keys. The words GOOD or BAD were presented at fixed-time intervals regardless of the participant's responses. In Experiment 1, only participants exposed to the negative reinforcement condition acquired superstitious behaviors. However, the observed asymmetry may not have been due to the polarity of consequences (positive vs. negative) but instead to the amount of time of goal states, because the period of the absence of BAD was longer than the period of the presence of GOOD. Experiment 2 varied the duration of word presentations to match the period of goal state between the positive and negative reinforcement conditions, and found that participants acquired superstitious behaviors equally under the two conditions. These results indicate that the duration of a consequence rather than its polarity is a critical factor controlling superstitious behaviors. The theoretical relationship between superstitious behavior and the illusion of control is discussed.

Running-based taste aversion learning in five strains of rats.

Although it is well known that voluntary wheel running works as an effective unconditioned stimulus to cause conditioned taste aversion (CTA) in several strains of rats, there is no study that explores strain differences in running-based CTA. The present study examines this issue with regard to five frequently used rat strains. Experiment 1 compared Sprague­Dawley versus Wistar rats from two suppliers, with the target taste being salty (NaCl + MSG) and then sweet (saccharin). Experiments 2, 3, and 4 tested rats of Wistar versus Long-Evans, Lewis versus Fischer, and Sprague­Dawley versus Lewis strains, respectively, with sweet and then salty solutions. None of the experiments showed any reliable strain differences in the strength of running-based CTA, suggesting the robustness of this learning phenomenon.

Calorie supply does not alleviate running-based taste aversion learning in rats.

Voluntary running establishes aversion to the paired taste in rats. A proposed mechanism underlying this taste aversion learning is energy expenditure caused by the running. The energy expenditure hypothesis predicts that running-based taste aversion should be alleviated by a calorie supply since this would compensate for the energy expended by running. Accordingly, running-based taste aversion would be less readily established to a caloric substance (20% sucrose solution) than to a noncaloric substance (0.2% sodium saccharin solution). Because the sucrose and saccharin aversions were equivalent in Experiment 1, the validity of the energy expenditure hypothesis was questioned. Experiments 2 and 3 also pose a problem for this hypothesis, as post-session calorie supply by glucose tablets failed to alleviate running-based aversion to salty water.

Overshadowing of running-based taste aversion learning by another taste cue.

Training rats with serial presentations of two taste solutions before confinement in an activity wheel (X-->A-->running) resulted in weak aversion to taste X, compared to a training procedure without the presentation of A. Demonstration of the overshadowing effect in the present study provides another parallel feature between running-based taste aversion learning and Pavlovian conditioning preparations including poison-based taste aversion learning. It also indirectly supports the claim that cue competition causes degraded contingency effect and cover-cue effect in rats' running-based taste aversion (Nakajima, 2008).

Feature-short and feature-long discrimination learning in the pigeon: conditional control of a two-event temporal map.

Eight pigeons were trained to peck an illuminated target key on discrete-trial fixed-interval schedules of reinforcement by food. Four birds were exposed to a feature-short (FS) task where a feature light signaled shortening of the forthcoming target-outcome interval from 30 to 15s, while the other four birds were exposed to a feature-long (FL) task where a feature light signaled extension of the forthcoming target-outcome interval from 15 to 30s. The discrimination performance measured by differential temporal distributions of pecks between featured and non-featured target trials suggested that the target-food temporal map was under conditional control of the feature light in both groups. The FS discrimination was more difficult to learn than the FL discrimination. This FS inferiority implies that our birds did not resort on the simple temporal discrimination by timing from the trial onset. The simple temporal discrimination account was also negated by the finding that increasing the feature-target gap did not have a predicted effect on the response distribution.

Forward conditioning with wheel running causes place aversion in rats.

Backward pairings of a distinctive chamber as a conditioned stimulus and wheel running as an unconditioned stimulus (i.e., running-then-chamber) can produce a conditioned place preference in rats. The present study explored whether a forward conditioning procedure with these stimuli (i.e., chamber-then-running) would yield place preference or aversion. Confinement of a rat in one of two distinctive chambers was followed by a 20- or 60-min running opportunity, but confinement in the other was not. After four repetitions of this treatment (i.e., differential conditioning), a choice preference test was given in which the rat had free access to both chambers. This choice test showed that the rats given 60-min running opportunities spent less time in the running-paired chamber than in the unpaired chamber. Namely, a 60-min running opportunity after confinement in a distinctive chamber caused conditioned aversion to that chamber after four paired trials. This result was discussed with regard to the opponent-process theory of motivation.