Effects of stimulus preexposure on the generalization of conditioned taste aversions in infant rats

Generalization of a conditioned taste aversion in infant rats and how this is affected by stimulus preexposure was investigated in a series of experiments. In Experiment 1 generalization of a conditioned aversion between two tastes (sweet and salty) was found, and the effect of tastes preexposure was a reduction in generalization (Experiment 2). However, when these tastes were combined with a common taste (acid) that was less (Experiment 3) or more intense (Experiment 3b), the effect of stimulus preexposure was a stronger generalization of the conditioned aversion. In this case, a reduction on generalization was again observed by increasing the number of preexposure trials to the taste compounds (Experiment 4). In all cases the generalization levels were directly related to the effect of stimulus preexposure on the acquisition rate of conditioning. It can be concluded that, with the appropriate parameters, a reduction of generalization of a conditioned taste aversion can be obtained after taste exposure in preweanling rats.     

Familiarization and cross-familiarization of wheel running and LiCl in conditioned taste aversion

Familiarization with an unconditioned stimulus (US) interferes with the learning of subsequent Pavlovian conditioned associations. We conducted a series of experiments exploiting this US preexposure effect to elucidate the underlying mechanism of conditioned taste aversion in rats induced by voluntary wheel running. Experiment 1 demonstrated that running-induced taste aversion was alleviated if rats had sufficient experience of running in advance. In Experiments 2A and 2B, preexposure to wheel running had no effect on subsequent taste aversion conditioning by lithium chloride (LiCl) injection. In Experiment 3, however, we observed a weak partial interference from the LiCl injection pretreatment to the subsequent conditioning by wheel running US. This US crossover effect suggests the possibility that wheel running and LiCl injection share a common or similar physiological mechanism in inducing taste aversion.     

Furosemide-induced food avoidance: evidence for a conditioned response

Furosemide (Furo) is a potent natriuretic drug that is often used experimentally to investigate the brain mechanisms underlying salt appetite. Within this experimental paradigm, however, Furo also has anorectic activity that has received only modest attention. In Experiment 1 we varied two things-administering a 10-mg dose of Furo in a single or a divided dose and preinjection exposure to a Na-free diet. In the 24 h after Furo, all four groups of rats reduced ingestion of Na-free diet. Both the division of the Furo dose and the preexposure to Na-free diet reduced the amount of food consumed even more than a single dose or continuous access to normal chow did. The fact that preexposure to Na-free diet increased the post-Furo anorexia implied an associative component to the phenomenon. Experiments 2 and 3 investigated the ability of Furo (2 and 10 mg) to serve as an unconditioned stimulus in taste aversion learning using 0.2 M sucrose as the conditioned stimulus. A saline (Sal) injection group served as control in both experiments. The results show that animals avoided sucrose when its ingestion was immediately followed by 10 mg Furo but not with 2 mg Furo or Sal. An aversion to sucrose did not develop when 10 mg Furo was administered the day prior to sucrose access. Thus, the suppressive effects of high-dose Furo on food intake might be due to a conditioned response.     

Differential effect of free intake versus oral perfusion of sucrose in conditioned taste aversion in rats.

Five experiments were designed to investigate LiCl-induced conditioned taste aversion (CTA) obtained in rats whether after free intake of a sucrose solution (active mode) or after forced administration through an intraoral cannula (passive mode). It was found in Experiment 1 that actively conditioned rats showed a slower extinction rate as revealed by repeated two-bottle tests (active testing) as opposed to passively conditioned ones. As these rats underwent a mode change between conditioning and testing, the differential extinction rate might have arisen from this change inducing a generalization decrement effect or acting as a contextual shift. In Experiment 2, no evidence for any generalization decrement was found. The possibility that the mode of sucrose delivery could have contextual properties in CTA through a "renewal test" after extinction and a latent inhibition experiment was further tested in Experiments 3 and 4. When active testing followed passive extinction, a CTA was afresh obtained in rats actively conditioned in active conditions. Latent inhibition was attenuated in rats preexposed in passive conditions and conditioned in active conditions (i.e., when a shift in the drinking mode occurred between preexposure and conditioning). In Experiment 5, intraoral perfusion was used in both groups. The active subjects had to nose poke for intraoral administration of sucrose. The yoked control passive subjects received simultaneously the same amount of sucrose. The levels of CTA differed also from the actively to the passively conditioned subjects. Results are discussed in terms of free intake activity acting as a contextual modulator of CTA.     

Taste aversion learning induced by forced swimming in rats

Two experiments demonstrated that forced swimming endowed rats with aversion to the taste solution consumed before the swimming. In Experiment 1, the rats given a trial of taste–swimming sequence drank less of the taste solution in a later test than did the rats given a taste-alone trial. The rats given a trial of taste–poisoning–swimming sequence, however, drank more of the taste solution in the testing than did the rats given a trial of taste–poisoning sequence. These results suggest that some effects of swimming (e.g., energy expenditure caused by physical exercise) induce conditioned taste aversion although they attenuate taste aversion conditioned by poisoning. The attenuation of poison-induced taste aversion by swimming has been reported in the literature, but the swimming-induced taste aversion is novel. Experiment 2, accordingly, was planned to confirm this phenomenon with a differential conditioning procedure, where one of two taste solutions was paired with swimming while the other was not. After a few repetitions of these two types of trials, the rats' intakes of these two solutions were differentiated to show that swimming has the ability to cause taste aversion.     

Signaling the unconditioned stimulus during the preexposure phase does not attenuate the unconditioned stimulus preexposure effect in preweanling rats

The unconditioned stimulus preexposure effect (US‐PE) is defined as an attenuation of the conditioned response after preexposure to the US prior to conditioning. Evidence exists that this effect can be weakened or eliminated by the presence of a signal predicting the US during the preexposure phase. This evidence has been found consistently across a variety of procedures in adult rats. The aim of the present study was to evaluate whether, in infant rats, signaling the US (LiCl) during preexposure with a salient cue (almond odor) attenuates the US‐PE. During the preexposure phase, preweanling rats received three (Experiment 1) or one (Experiment 2) preexposures to LiCl, preceded by exposure to almond odor. Appropriate control groups were also included in these experiments. After preexposure, two conditioning trials were carried out in which subjects were given LiCl after saccharin consumption. During preexposure, three (Experiment 1a), although not one (Experiment 2a), contingent exposures to almond odor and LiCl resulted in a strong odor aversion. Extinction of the learned taste aversion was facilitated by prior experience with LiCl (Experiments 1b and 2b). This effect was observed regardless of whether or not LiCl was signaled by the almond odor. These results do not coincide with the associative hypotheses proposed to explain the US‐PE, nor are they concurrent with alternative explanations based on the learned helplessness phenomenon. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 808–817, 2012     

Differential effects of electrical stimulation of amygdala, caudate-putamen or substantia nigra pars compacta on taste aversion and passive avoidance in rats

The effect of unilateral, low-intensity subseizure electrical stimulation of the basolateral nucleus of the amygdala (ABL), caudate-putamen (CD) or substantia nigra pars compacta (SNC) on the acquisition and retention of a conditioned taste aversion and a step-down passive avoidance response were compared in two separate experiments. In Experiment 1 electrical stimulation of the ABL while rats were drinking saccharin prior to poisoning with LiCl disrupted conditioned taste aversion. Stimulation of the CD or SNC had no disruptive effect on taste aversion. In contrast, stimulation at all 3 brain loci disrupted the retention of a passive avoidance response in Experiment 2. The implications of these data for the hypothesis of dual neural control systems for shock avoidance behavior and taste aversion, are discussed.     

Recall of a previously acquired conditioned taste aversion in rats following lesions of the area postrema

A conditioned taste aversion was produced by pairing a novel sucrose solution with either 3 mEq lithium chloride or with 100 rad gamma radiation in rats with the area postrema intact. Lesions of the area postrema were then made in half of the rats exposed to each treatment and in rats that were not treated with the unconditioned stimulus. When tested for a conditioned taste aversion, all treated rats showed a significant aversion to the sucrose solution compared to the untreated control rats. There were no significant differences between rats with area postrema lesions and those with the area postrema intact, indicating that the lesions had no effect on the recall of the previously acquired aversion. The results are interpreted as being consistent with the hypothesis that the role of the area postrema in taste aversion learning is to monitor blood and cerebrospinal fluid for potential toxins and to transmit that information to the central nervous system.     

Latent Inhibition and Conditioning in Rat Strains Which Show Differential Prepulse Inhibition

Latent inhibition (LI) is the retardation of associative conditioning resulting from preexposure of the conditioned stimulus (CS) alone prior to conditioning. Schizophrenic patients show deficient prepulse inhibition (PPI) and, at least acutely, deficient LI as well. We recently found that Brown Norway (BN) rats show a PPI deficit compared to Wistar-Kyoto (WKY) rats. If PPI and LI depend on neural processes with common genetic substrates, then LI should be deficient in BN rats as well. Here, LI of a conditioned taste aversion was examined in BN and WKY rats. One group from each strain was preexposed to a saccharin-flavored solution (CS) the day prior to conditioning. For taste aversion conditioning, these two groups again consumed saccharin and were injected with lithium chloride (unconditioned stimulus) 10 min later. A second group from each strain was not preexposed to the CS and was treated identically during conditioning, while a third group was not conditioned (injected with sodium chloride). To test for taste aversion conditioning, saccharin was offered for 20 min/day for 3 days. Nonconditioned BN and WKY rats consumed equal amounts of saccharin on test days. In both strains, conditioned rats showed a saccharin aversion. However, conditioning was less robust in BN than in WKY rats. WKY rats showed good LI of the conditioned taste aversion in that preexposed WKY rats consumed significantly more saccharin on test days than conditioned, nonpreexposed WKY rats. Preexposed BN rats did not consume significantly more saccharin on test days than conditioned, nonpreexposed BN rats. The previously reported deficiency in PPI in the BN rats was confirmed here 1 week after the taste aversion experiment. These results suggest that BN rats show deficient LI as well as PPI and display poor associative learning, a trait also reported in schizophrenia.     

Vasopressin deficiency abolishes a sexually dimorphic behavior in Brattleboro rats.

The role of vasopressin (VP) in a sexually dimorphic behavior, the extinction of a conditioned taste aversion, was investigated in male and female rats of three different genotypes. This behavior was examined with a two bottle test in the wild-type Long-Evans (LE) rats, and then in partially VP deficient heterozygous (HET-BB) and completely VP deficient homozygous (HO-BB) Brattleboro rats. In Experiment 1, non-deprived male and female LE rats were given aversions to a sucrose solution by pairing it with a LiCl injection. The rate of extinction of the aversion upon reexposure to ad lib sucrose solution was examined and observed to be sexually dimorphic. Female LE rats extinguished at a significantly more rapid rate than males. Experiment 2 compared HET-BB and HO-BB male and female rats using the same paradigm. Neither of these VP-deficient groups showed sexual dimorphism of the extinction behavior. The data suggest that intact VP levels are necessary to observe the expression of this sexually dimorphic behavior.     

Alcohol aversion generalization in rats: specific disruption of taste and odor cues with gustatory neocortex or olfactory bulb ablations

Rats with ablations of the gustatory neocortex (Experiment 1) and rats with olfactory bulb ablations (Experiment 2) were compared with normal rats for aversion generalization to both single taste solutions (sucrose, sodium chloride, quinine hydrochloride, hydrochloric acid) and compound taste solutions (pairs of the four single tastants) following alcohol aversion training. All rats acquired equal and strong alcohol aversions. Control rats showed consistent aversion generalization to both the sucrose + quinine and the sucrose + hydrochloric acid solutions; no significant generalization occurred to the single tastants except a weak generalization to sucrose in Experiment 2. Rats with gustatory neocortical ablations failed to show aversion generalization to any of the taste solutions. Rats with olfactory bulbectomies displayed the same aversion generalization functions as control rats but exhibited significantly faster extinction of the alcohol aversion than did the trained control rats. Results from the present experiments suggest that during alcohol aversion learning, rats lacking gustatory neocortex use odor cues (no taste generalization), whereas rats lacking olfactory bulbs utilize taste cues (normal taste generalization).     

Backward conditioning of tumor necrosis factor-α in a single trial: changing intervals between exposures to lipopolysaccharide and saccharin taste

The current study examined the effect of backward conditioning with three different time intervals between exposures to lipopolysaccharide (LPS) as the unconditioned stimulus (US) and saccharin taste in water as the potential conditioned stimulus (CS). Forty-eight naïve female BALB/c mice at three months of age served as subjects, divided into six groups. Four groups were assigned to Experiment 1 for the tumor necrosis factor alpha (TNF-α) measure, and the remaining two groups were used in Experiment 2 to measure taste aversion behavior. Both experiments employed a single trial. The timing of introduction to the saccharin taste varied between 3 min, 7 h, and 24 h following an LPS injection in Experiment 1. Experiment 2 employed the three-minute interval only. These intervals correspond to distinct immunological, physiological, and behavioral events induced by LPS. On the day after re-exposure to the saccharin taste, the TNF-α groups were challenged with LPS to test the LPS tolerance response. While backward conditioning of taste aversion behavior was not observed, some evidence of conditioned TNF-α response and subsequent development of LPS tolerance was observed with backward conditioning in a single trial. This exploratory study demonstrated that the effect of backward conditioning on conditioned TNF-α response and LPS tolerance response in a single trial depended on the timing of when a CS is presented after LPS exposure.     

Effects of basolateral amygdala lesions on taste aversions produced by lactose and lithium chloride in the rat

In Experiment 1, intact rats were given either lactose or sucrose solutions. Although on first exposure they readily consumed lactose, its ingestion produced a conditioned taste avoidance which was partly extinguished by repeated sucrose exposure after lactose conditioning. In Experiment 2, rats with large bilateral electrolytic lesions of the basolateral amygdala and those with either sham or no operations were given two pairings of saline with LiCl injections (upper gastrointestinal tract discomfort) and in a separate condition access to high levels of lactose (lower gastrointestinal tract discomfort). Conditioned taste avoidances were measured both by two-bottle tests and by video recordings of the rats' orofacial and somatic responses. The lesions attenuated LiCl-induced taste aversion but not lactose-induced taste avoidance, results demonstrating that taste avoidance can occur without the basolateral amygdala. The results suggested that aversions based on distaste can be distinguished from avoidances based on danger, not only in terms of orofacial responses but also in terms of their neuroanatomical substrate.     

Multiple remote-US preexposures and the blocking effect produced by a proximal-US

Weanling, young-adult, and old-age Wistar albino rats were used to determine whether number of unconditioned stimulus (US) presentations, given 24 h or more (remote preexposure) prior to conditioning, alters the blocking effect of a single-US preexposure given 2 h before (proximal) taste aversion conditioning. As the number of remote-US preexposures increased from 0 to 6, the ability of the proximal-US preexposure to block conditioning initially increased then decreased for all age groups. Of the models put forth to explain US preexposure effects on conditioned taste aversion (CTA), only Wagner's information processing model adequately explained the reduction of the blocking effect of the proximal-US preexposure produced as a result of increasing remote-US preexposures.     

Estrogen increases the taste threshold for sucrose in rats

Anecdotal and empirical evidence suggests that females' preferences for sweet foods are affected by hormonal fluctuations across the reproductive cycle. In rats, the preference for sweet foods may involve estrogen-mediated changes in response to the taste of sweets. Our recent work showed that ovariectomized female rats lick less to dilute sucrose solutions when given estrogen than when given the oil vehicle. These findings suggest that estrogen decreases the preference for less concentrated sucrose solutions; however, an alternative explanation is that estrogen interferes with the ability to detect dilute sucrose solutions. To distinguish between these possibilities, we conditioned a taste aversion to 0.2 M sucrose in ovariectomized rats by pairing it with injection of LiCl and then examined the generalization of that taste aversion to 0.075 and 0.025 M sucrose solutions during estrogen or oil treatment. Oil-treated rats generalized the LiCl-induced aversion conditioned to 0.2 M sucrose to both 0.075 and 0.025 M sucrose. Estrogen-treated rats generalized the LiCl-induced taste aversion to 0.075 M sucrose but not to 0.025 M sucrose. Moreover, two weeks later, when estrogen had cleared the system, both groups generalized the aversion to both 0.075 and 0.025 M sucrose. These results show that estrogen affects the ability to discriminate dilute sucrose from water and suggest that estrogen may have short-term effects on the detection threshold for sucrose taste in rats.     

Taste reactivity as a dependent measure of the rapid formation of conditioned taste aversion: a tool for the neural analysis of taste-visceral associations

Several explanations may account for deficits in the ability of animals to form taste aversions following neural manipulations. These encompass impairments in conditioned stimulus (CS) and unconditioned stimulus (US) processing, conditioned response (CR) measurement, and expression, memory, and taste-visceral integration. A behavioral procedure that aids in the distinction between some of these possibilities is presented. In Experiment 1, 10 rats received seven intraoral (IO) infusions of sucrose (30 s, 0.55 ml) spaced every 5 min starting immediately after the injection of 3.0 mEq/kg of lithium chloride (LiCl). Control rats (n = 12) were treated identically except that they were injected with sodium chloride (NaCl). Oromotor and somatic taste reactivity behaviors were videotaped and analyzed. Lithium-injected rats systematically decreased their ingestive taste reactivity behavior over time, whereas aversive behavior increased. Control rats maintained high and stable levels of ingestive responding and demonstrated virtually no aversive behavior over the 30-min period following sodium injection. Rats were tested several days later for the presence of a conditioned taste aversion (CTA). Rats previously injected with lithium during sucrose infusions demonstrated significantly more aversive behavior than the control group, which demonstrated none. There were no differences in the level of ingestive behavior displayed by the two groups on the CTA test. Experiment 3 revealed that when similarly treated rats were tested for a CTA while in a lithium-induced state, a difference in the ingestive behavior between the two groups was observed. In Experiment 2, naive rats were injected with either NaCl or LiCl but did not receive their first sucrose infusion until 20 min later. These rats also received sucrose infusions at 25 and 30 min postinjection. There were no differences in the taste reactivity behavior displayed by lithium- or sodium-injected rats during any of the sucrose infusions. Collectively, these findings indicate that rats dramatically change their oromotor responses to sucrose during the period following LiCl administration, provided that the infusions start immediately after injection. Furthermore, this time-related behavioral change is predominantly attributable to associative processes. This paradigm can be useful in distinguishing between neural manipulations that affect the establishment of taste-visceral associations from others that affect the animal's ability to retain such associations over the commonly employed 24-hr conditioning-test interval.     

Aversive consequences of jejunoileal bypass in the rat: a conditioned taste aversion analysis

Jejunoileal bypass (JIB) surgery reduces food intake and body weight in obese humans and rats. Human bypass patients report visceral discomfort following surgery, and the present study assessed the aversive consequences of JIB in rats using a conditioned taste aversion paradigm. In Experiment 1 rats given a cherry-flavored solution immediately after JIB surgery subsequently displayed a strong aversion to the cherry flavor compared to Bypass and Sham-Bypass control groups. Rats in Experiment 2 were familiarized with cherry solution prior to surgery and they did not display an aversion to the solution after receiving a JIB. In Experiment 3, Bypass rats who developed a cherry flavor aversion after JIB subsequently lost this aversion following reconnection of their intestinal tract. The rats in Experiment 4 displayed an aversion to a saccharin-flavored chow that was eaten shortly after JIB surgery, although the aversion was not as pronounced as that obtained with the cherry solution. The results suggest that JIB produces a persisting malaise in rats that may contribute to the feeding and weight inhibitory effects of the operation.     

Temporal coding of sensation: mimicking taste quality with electrical stimulation of the brain

Two experiments suggested that the temporal pattern of a taste response in the brain can convey meaningful information. In Experiment 1, rats avoided lick-contingent electrical stimulation of the nucleus of the solitary tract (NTS; the first synaptic relay for taste) when the temporal pattern of pulses mimicked the electrophysiological response to quinine, but not when the temporal pattern was randomized. In Experiment 2, rats avoided lick-contingent electrical stimulation of the NTS that mimicked the temporal pattern of a sucrose response following stimulation-illness pairings. This aversion generalized to sucrose but not to the other tastants; extinction of the aversion to electrical stimulation also extinguished the aversion to sucrose. Results replicate and extend previous findings (P. M. Di Lorenzo & G. S. Hecht, 1993).     

Amygdalectomy induced deficits in conditioned taste aversion: possible pituitary-adrenal involvement

Bilateral lesions to the amygdala in rats impaired a conditioned taste aversion produced by pairing the taste of sweetened milk with lithium chloride (Experiment 1). A second experiment investigated the role of adrencorticotropin (ACTH) in the amygdala lesion-induced deficits in conditioned taste aversion. ACTH injection on the day of conditioning was without effect in either sham or amygdala lesioned animals. ACTH injection on the day of testing was without an effect in sham animals. However, ACTH injection augmented the avoidance behavior of amygdala lesioned subjects (Experiment 2). These data suggest a pituitary-adrenal involvement in the amygdalectomy-induced deficits in conditioned taste aversion.