Effects of a flavor-placement reversal test after different modalities of taste aversion learning

Taste aversion learning is induced through two different behavioral procedures: a short-term or concurrent (two-daily flavors) and a long-term or sequential (one-daily flavor) procedure. For the concurrent group of animals, two gustatory/olfactory stimuli are presented separately but at the same time on a daily basis. One is paired with simultaneous intragastric administration of hypertonic NaCl and the other with physiological saline. For the sequential group, the two stimuli are presented on alternate days, one of them followed by intragastric injection of the aversive stimulus and the other by saline, both after a delay of 15 min. The two groups learned the task, but when they were subjected to a flavor-placement reversal test only the sequential group was successful in achieving it. In a second experiment, three groups of animals had to learn concurrent or sequential discrimination tasks (with either simultaneous or delayed administration of the visceral stimulus) using only spatial/proprioceptive cues. The data show that none of the groups learned them under these conditions. The results are discussed in terms of the different modalities of learning. Short-term and long-term taste aversion learning are different in the anatomical structures involved, the number of trials required for acquisition and, as shown in this paper, flexibility.     

Electrolytic lesions of the pedunculopontine nucleus disrupt concurrent learned aversion induced by NaCl

Bilateral electrolytic lesions in the pedunculopontine nucleus (PPN) impair acquisition of short-term, or concurrent, Taste Aversion Learning (TAL) in rats. This type of TAL is characterized by the daily presentation of two different flavor stimuli at the same time, one associated with simultaneous intragastric administration of an aversive product (hypertonic NaCl) and the other with physiological saline. Sham-lesioned control animals learn this taste discrimination task, but both lesioned animals and control animals learn a long-term, or delayed, TAL task in which each gustatory stimulus is presented individually every other day and the intragastric products, LiCl (0.15 M) and physiological saline, are administered after a 15-min delay. These results are analyzed in the context of the cerebellar circuits involved in learning and in relation to the two TAL modalities described above.     

Conditioning Method Dramatically Alters the Role of Amygdala in Taste Aversion Learning

Although an important role for the amygdala in taste aversion learning has been suggested by work in a number of laboratories, results have been inconsistent and interpretations varied. The present series of studies reevaluated the role of the amygdala in taste aversion learning by examining the extent to which conditioning methods, testing methods and lesioning methods, influence whether amygdala lesions dramatically affect conditioned taste aversion (CTA) learning. Results indicated that when animals are conditioned with an intraoral (I/O) taste presentation, lesions of amygdala eliminate evidence of conditioning whether animals are tested intraorally or with a two-bottle solution presentation. Dramatic effects of amygdala lesions on CTA learning were seen whether lesions were made electrolytically or using an excitotoxin. In contrast, when animals were conditioned using bottle presentation of the taste, electrolytic lesions attenuated CTAs but did not eliminate them, and excitotoxic lesions had no effect. These results are consistent with the hypothesis that neural structures critical for CTA learning may differ depending on the extent to which the method of conditioned stimulus delivery incorporates a response component.     

Gastrointestinal reactivity in rats lacking anterior insular neocortex

Behavioral and physiological studies have shown that the insular neocortex participates in a wide variety of special visceral processes, in particular, the higher-order integration of taste stimuli and the regulation of autonomic activity. The present experiment examined the involvement of the anterior insular (gustatory) neocortex (AIGN) in gastrointestinal reactivity and taste learning in rats by the use of a modified taste aversion training procedure. Normal rats and rats lacking AIGN demonstrated similar "illness thresholds" to the early onset symptoms of ingested LiCl. Conversely, animals lacking AIGN showed significant impairments in taste aversion learning ability. From a consideration of several research findings it is concluded that animals lacking AIGN can normally perceive tastes and illness, but these animals experience reliable impairments in taste aversion learning ability.     

Learned preferences induced by electrical stimulation of a food-related area of the parabrachial complex: effects of naloxone

Electrical stimulation of the External Lateral Parabrachial Subnucleus (LPBe), a food-related area, induced behavioral preferences for associated stimuli in a taste discrimination learning task. Although this stimulation appeared to be ineffective to elicit standard lever press self-stimulation, it induced place preference for one of two training compartments of a rectangular maze in which animals (adult male Wistar rats) received concurrent electrical brain stimulation. In subjects that consistently showed a preference behavior in different trials, administration of the opioid antagonist naloxone (4 mg/ml/kg) blocked concurrent learning when the test was made in a new maze but not in the same maze in which animals had learned the task. These results are discussed in terms of the possible participation of the LPBe subnucleus in different natural and artificial brain reward systems.     

Temporary basolateral amygdala lesions disrupt acquisition of socially transmitted food preferences in rats

Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in chemosensory learning remains somewhat controversial. In particular, it has been suggested that the amygdala may not be involved in a form of chemosensory learning that has recently received a substantial amount of study-socially transmitted food preference (STFP). Here, we provide evidence for this involvement by pharmacologically inactivating the basolateral amygdala bilaterally during STFP training. The same inactivation sites that impaired taste aversion learning eliminated the normally conditioned preference for a food smelled on a conspecific's breath. Impairments of learned preference persisted even in testing sessions in which BLA was not inactivated, and learning was normal when the BLA was inactivated only during testing sessions; thus, the impairment was a true acquisition deficit. In conjunction with previous results from other paradigms, therefore, our data suggest that the amygdala is vital for learning procedures involving pairings of potent and arbitrary chemosensory stimuli.     

Intragastric copper sulfate produces a more reliable conditioned taste aversion in vagotomized rats than in intact rats

Although copper sulfate is an emetic stimulus, preliminary experiments failed to obtain a taste aversion in intact rats following intragastric administration as had been previously reported in the literature. Several experiments were therefore run to further investigate the capacity of intragastric copper sulfate to function as an unconditioned stimulus for taste aversion learning and the role of the vagus in mediating that learning. The results of the first series of experiments showed that intragastric administration of copper sulfate (5 mg/kg X 5H2O) was more effective in reliably producing a taste aversion in vagotomized rats than in sham-operated control rats. The second experiment examined the effects of area postrema lesions on the acquisition of a taste aversion produced by intragastrically administered copper sulfate in vagotomized rats. The results indicated that the taste aversion observed following treatment with intragastric copper sulfate in vagotomized rats could be prevented by lesions of the area postrema. The present results indicate that intragastric administration of copper sulfate is a more reliable unconditioned stimulus for taste aversion learning in vagotomized rats than in intact rats. It is not certain what factors might account for the discrepant results between the present experiments and previously published research.     

Dorsomedial pallium lesions impair taste aversion learning in goldfish

The present work shows that the dorsomedial telencephalic pallium of teleost fish, proposed as homologous to the amygdala of mammals, is involved in taste aversion learning (TAL). To analyze the behavioral properties of TAL in goldfish, in Experiment 1, we used a delayed procedure similar to that employed with mammals, which consists of the presentation of two flavors on different days, one followed by lithium chloride and the other by saline, both after a 10-min delay. The results showed that goldfish developed a strong aversion to the gustatory stimulus followed by visceral discomfort and that, as in mammals, this learning was rapidly acquired, highly flexible and maintained for a long time. Experiment 2 showed that dorsomedial pallium lesions and the ablation of the telencephalic lobes impaired the acquisition of taste aversion in goldfish, whereas damage to the dorsolateral pallium (hippocampus homologue) or cerebellar corpus did not produce significant changes in this learning. Experiment 3 showed that these TAL deficits were not due to a lesion-related disruption of taste discrimination; goldfish with telencephalon ablation were able to learn to distinguish between the two tested flavors in a differential conditioning procedure. These functional data demonstrate that the dorsomedial pallium in teleosts is, like the amygdala, an essential component of the telencephalon-dependent taste aversion memory system and provide further support concerning the homology between both structures.     

Taste-mediated potentiation of noningestional stimuli in rats

Holtzman rats drank saccharin in a distinctive environmental chamber prior to lithium-induced toxicosis. This treatment was administered four times. These animals subsequently drank less water or familiar saline in the chamber than animals which received water in the environment during conditioning. In addition, these environmental stimuli blocked the formation of a lithium-mediated coffee aversion more if they were conditioned in the presence of saccharin than if they were conditioned in the presence of water. Such differential blocking provided further evidence that the presence of a taste during conditioning facilitated aversion learning to the environmental chamber.     

Hippocampal inactivation enhances taste learning

Learning tasks are typically thought to be either hippocampal-dependent (impaired by hippocampal lesions) or hippocampal-independent (indifferent to hippocampal lesions). Here, we show that conditioned taste aversion (CTA) learning fits into neither of these categories. Rats were trained to avoid two taste stimuli, one novel and one familiar. Muscimol infused through surgically implanted intracranial cannulae temporarily inactivated the dorsal hippocampus during familiarization, subsequent CTA training, or both. As shown previously, hippocampal inactivation during familiarization enhanced the effect of that familiarization on learning (i.e., hippocampal inactivation enhanced latent inhibition of CTA); more novel and surprising, however, was the finding that hippocampal inactivation during training sessions strongly enhanced CTA learning itself. These phenomena were not caused by specific aspects of our infusion technique--muscimol infusions into the hippocampus during familiarization sessions did not cause CTAs, muscimol infusions into gustatory cortex caused the expected attenuation of CTA, and hippocampal inactivation caused the expected attenuation of spatial learning. Thus, we suggest that hippocampal memory processes interfere with the specific learning mechanisms underlying CTA, and more generally that multiple memory systems do not operate independently.     

Taste aversion learning: simulation of interference with the gustatory cue during conditioning

Rats were taught an aversion to a sucrose taste cue of varying strengths. The concentration of the sucrose solution was either, 10, 7.5, 5, 2.5, 1, 0.5, or 0.25% which the animals drank for 5 min. Thirty minutes later they were poisoned with lithium chloride. On the test day all animals had access to a 10% sucrose solution regardless of the concentration they had drunk on the conditioning day. Animals conditioned with a 10, 7.5, or 5% sucrose cue subsequently displayed an identically strong aversion to the 10% cue. Only those animals conditioned with a sucrose cue which was 1% or less displayed a significantly weaker aversion to the 10% cue. The results are discussed in terms of the theory that interference with taste aversion learning by such agents as pentylenetetrazol and electroconvulsive shock may have their effect by disrupting the gustatory engram. If this assumption is correct then it suggests that the memory of the gustatory cue may be stored, at least prior to poisoning, in a quite labile state and an apparently limited disruption of taste aversion learning may in fact represent a substantial amnesic effect.     

Capsaicin-sensitive afferent vagal fibers are involved in concurrent taste aversion learning

Taste aversion learning (TAL) is a type of learning characterized by rejection of a gustatory/flavor stimulus as a consequence of its pairing with visceral discomfort and malaise. TAL can be established in the laboratory by two different behavioral procedures, concurrent or sequential. Neural mechanisms of these learning modalities remain to be elucidated, but several studies have discussed the implication of various anatomical structures, including the vagus nerve. The aim of this study was to examine the role of capsaicin-sensitive vagal afferent fibers in concurrent (Experiment 1) and sequential (Experiment 2) TAL in Wistar rats. Results showed that perivagal administration of capsaicin (1mg of capsaicin dissolved in 1ml of vehicle (10% Tween 80 in oil)) blocked acquisition of concurrent but not sequential TAL. These data support the hypothesis of two different modalities of TAL mediated by distinct neurobiological systems, with vagal nerve participation only being essential in concurrent TAL.     

The role of the insular cortex in taste function

In spite of over 30 years of research, the role of the Insular Cortex (IC) in taste memory still remains elusive. To study the role of the IC in taste memory, we used conditioned taste aversion (CTA) for two different concentrations of saccharin; 0.1% which is highly preferred, and 0.5% which is non-preferred. Rats that had been IC lesioned bilaterally with ibotenic acid (15 mg/ml) before CTA showed significant learning impairments for saccharin 0.1% but not for saccharin 0.5%. To test CTA memory retention, rats lesioned a week after CTA training became completely amnesic for saccharin 0.1% yet only mildly impaired for saccharin 0.5%. Interestingly, the resulting preference for either concentration matched that of IC lesioned animals when exposed to either saccharin solution for the first time, but not those of sham animals, implying that IC lesions after CTA for either saccharin solution rendered complete amnesia, irrespective of the original preference. Our data indicate that an intact IC is essential for CTA learning and retention, as well as for an early neophobic response, but not for taste preference itself. Our data supports a model where the IC is involved in general taste rejection.     

Disruption of conditioned taste aversion: evidence that ECS weakens the gustatory engram

Two experiments are reported concerning the neural substrate of conditioned taste aversion (CTA) and the amnesic mechanisms involved when such learning is disrupted by electroconvulsive shock (ECS). Subjects were adult male rats. In the first experiment it is demonstrated that an aversion established to a 2.5% sucrose solution can simulate the learning loss reported in earlier studies which was caused by interpolating ECS between tasting and illness when the aversion was established using a 10% sucrose cue. It is concluded that if ECS acts to disrupt the memory of the taste cue, it possibly reduces it to only about one-quarter of its original strength, a substantial deficit not readily apparent simply from the degree of aversion displayed. In the second experiment, CTAs were established using either a 2.5% sucrose cue or a 10% cue with ECS interpolated during the taste-illness interval. Animals in the two groups were subsequently confronted with a range of sucrose stimuli and their respective aversions were compared. Near identical responses were observed under all conditions tested. These findings are consistent with the theory that ECS disrupts CTA by weakening the gustatory engram.     

Augmentation of taste conditioning by a preconditioned odor.

Five experiments explored facilitated taste-aversion conditioning (odor-mediated taste augmentation), using rats that experienced odor (A) and taste (X) in an A+/AX+ design. Augmentation occurred when the stimuli were presented simultaneously during AX+ conditioning, and significantly weaker conditioning occurred after a sequential presentation (Experiment 1). Experiments 2 and 3 demonstrated that augmented conditioning decreased if the odor aversion was reduced through preexposure or extinction following A+ conditioning. A second-order conditioning explanation was not supported by the results of Experiment 4. Experiment 5 showed that extinction of the odor aversion after AX+ conditioning did not alter the strength of the augmented taste aversion. Odor-mediated taste augmentation is similar to potentiation, in which odor and taste cues operate in a synergistic, not competitive, manner.     

Arousal and activity level of rats with lesions in the dorsal hippocampus.

The effect on gross locomotor activity of irrelevant stimuli, prior exposure to these stimuli and two dosages of amphetamine were assessed on rats with lesions in the dorsal hippocampus. These animals were significantly more active post-operatively than sham-lesioned subjects. Prior exposure to the irrelevant stimuli increased post-operative differentiation between stimuli, whereas the introduction of amphetamine had the reverse effect. Changes in locomotor activity occurred at lower dosages of amphetamine than in previous studies, suggesting that the irrelevant stimuli have an arousal effect which acts additively with amphetamine and hippocampal impairment.     

Selective associations in one-day-old rats: taste-toxicosis and texture-shock aversion learning

One-day-old rats learned aversions to a novel taste paired with lithium-induced distress and to a tactile stimulus paired with brief electric shocks. However, aversions did not develop when taste was paired with shock or when the tactile stimulus was paired with lithium treatment. The aversions occurred only when lithium treatment immediately followed taste exposure and when shock was concurrent with exposure to the tactile stimulus. These findings indicate that selective associations in aversion learning are mediated by innate mechanisms that govern conditioning in the absence of extensive ontogenetic experience. The present research also shows that selective associations are sufficient for the occurrence of long-delay learning.     

Involvement of the rat anterior cingulate cortex in control of instrumental responses guided by reward expectancy

The anterior cingulate cortex (ACC) plays a critical role in stimulus-reinforcement learning and reward-guided selection of actions. Here we conducted a series of experiments to further elucidate the role of the ACC in instrumental behavior involving effort-based decision-making and instrumental learning guided by reward-predictive stimuli. In Experiment 1, rats were trained on a cost-benefit T-maze task in which they could either choose to climb a barrier to obtain a high reward (four pellets) in one arm or a low reward (two pellets) in the other with no barrier present. In line with previous studies, our data reveal that rats with quinolinic acid lesions of the ACC selected the response involving less work and smaller reward. Experiment 2 demonstrates that breaking points of instrumental performance under a progressive ratio schedule were similar in sham-lesioned and ACC-lesioned rats. Thus, lesions of the ACC did not interfere with the effort a rat is willing to expend to obtain a specific reward in this test. In a subsequent task, we examined effort-based decision-making in a lever-press task where rats had the choice between pressing a lever to receive preferred food pellets under a progressive ratio schedule, or free feeding on a less preferred food, i.e. lab chow. Results show that sham- and ACC-lesioned animals had similar breaking points and ingested comparable amounts of less-preferred food. Together, the results of Experiment 1 and 2 suggest that the ACC plays a role in evaluating how much effort to expend for reward; however, the ACC is not necessary in all situations requiring an assessment of costs and benefits. In Experiment 3 we investigated learning and reversal learning of instrumental responses guided by reward predictive stimuli. A reaction time (RT) task demanding conditioned lever release was used in which the upcoming reward magnitude (five vs. one food pellet) was signalled in advance by discriminative visual stimuli. Results revealed that rats with ACC lesions were able to discriminate reward magnitude-predictive stimuli and to adapt instrumental behavior to reversed stimulus-reward magnitude contingencies. Thus, in a simple discrimination task as used here, the ACC appears not to be required to discriminate reward magnitude-predictive stimuli and to use the learned significance of the stimuli to guide instrumental behavior.     

Interference with ingestional aversion learning produced by preexposure to the unconditioned stimulus: Associative and nonassociative aspects

Preconditioning exposure to a lithium chloride unconditioned stimulus (US) interferes with the subsequent conditioning of a taste aversion. Multiple US preexposures produce a long-lasting or durable interference with aversion learning, whereas a single US exposure produces a transient interference effect. The present experiments demonstrate that the durable US preexposure effect is substantially reduced if the method of drug treatment (infusion versus injection of the drug into the peritoneal cavity) or the spatial cues present during drug treatment (home cage versus a distinctive environment) are changed between the preexposure and taste conditioning phases of the experiment. In contrast, these manipulations do not attenuate the proximal/transient US preexposure effect. These findings indicate that different mechanisms are responsible for the two US preexposure effects. The results are consistent with previous suggestions that the durable effects of lithium preexposure are due to associative interference produced by the exteroceptive stimuli that accompany drug administrations and indicate that the proximal/transient US preexposure effect is mediated by nonassociative mechanisms.