Effects of excitotoxic brain lesions on taste-mediated odor learning in the rat

The association learning between taste and odor is important in ingestive behavior. For a better understanding of this learning, we have developed a convenient and useful paradigm to assess the taste-mediated odor learning. In the training session, Wistar male rats drank water from two bottles in their home cages and from eight small glass dishes. In the learning session they were exposed in their home cages and also in a circular open-field apparatus to 0.005 M Na-saccharin and 0.02 M quinine hydrochloride which contained either banana or almond odors. One learning trial consisted of this pair of exposures. The preceding behavioral experiment has shown that these two odors are not aversive and are differentially perceived by rats. In the test session, the animals were put in the open-field apparatus equipped with eight dishes: four contained water with banana, and another four, with almond. Normal control rats preferred to drink water with the odor previously associated with saccharin. Stronger and more persistent preference was attained after two or three learning trials. To elucidate the brain sites responsible for this taste-mediated odor learning, the same procedure was assessed on brain-lesioned rats. Rats with lesions in the amygdala showed rapid extinction of preference to the saccharin-associated odor, whereas control rats did not. However, rats with lesions in the insular cortex showed retention of learning similar to that of the control rats. Rats with lesions in the sulcal prefrontal or cingulate cortices showed moderate disruptive effects on preference to the saccharin-associated odor. In conclusion, the odor learning established in our experimental paradigm is based on the association between the quality of odor and hedonics of taste. The amygdala may play a role in the formation, at least in the retention process, of this taste-odor association learning.     

Potentiation of latent inhibition

Rats were given exposure either to an odor (almond) or a compound of odor plus taste (almond plus saline), prior to training in which the odor served as the conditioned stimulus. It was found, for both appetitive and aversive procedures, that conditioning was retarded by preexposure (a latent inhibition effect), and the extent of the retardation was greater in rats preexposed to the compound (i.e., latent inhibition to the odor was potentiated by the presence of the taste). In contrast, the presence of the taste during conditioning itself overshadowed learning about the odor. We argue that the presence of the salient taste in compound with the odor enhances the rate of associative learning, producing a rapid loss in the associability of the odor. This loss of associability will generate both overshadowing and the potentiation of latent inhibition that is observed after preexposure to the compound.     

Does taste or odor activate the same brain networks after retrieval of taste potentiated odor aversion?

When simultaneous presentation of odor and taste cues precedes illness, rats acquire robust aversion to both conditioned stimuli. Such a phenomenon referred to as taste-potentiated odor aversion (TPOA) requires information processing from two sensory modalities. Whether similar or different brain networks are activated when TPOA memory is retrieved by either the odor or the taste presentation remains an unsolved question. By means of Fos mapping, we investigated the neuronal substrate underlying TPOA retrieval elicited by either the odor or the taste conditioned stimulus. Whatever the sensory modality used to reactivate TPOA memory, a significant change in Fos expression was observed in the hippocampus, the basolateral nucleus of amygdala and the medial and the orbito-frontal cortices. Moreover, only the odor presentation elicited a significantly higher Fos immunoreactivity in the piriform cortex, the entorhinal cortex and the insular cortex. Lastly, according to the stimulus tested to induce TPOA retrieval, the BLA was differentially activated and a higher Fos expression was induced by the odor than by the taste in this nucleus. The present study indicates that even if they share some brain regions, the cerebral patterns induced by either the odor or the taste are different. Data are discussed in view of the relevance of each conditioned stimulus to reactivate TPOA memory and of the involvement of the different labeled brain areas in information processing and TPOA retrieval.     

Does the olfactory cue activate the same brain network during aging in the rat after taste potentiated odor aversion retrieval?

Depending on the brain networks involved, aging is not accompanied by a general decrease in learning and memory capabilities. We demonstrated previously that learning and retrieval of taste potentiated odor aversion (TPOA) is preserved, and even slightly improved, in senescent rats showing some memory deficiencies in cognitive tasks (Dardou, Datiche, & Cattarelli, 2008). TPOA is a particular behavior in which the simultaneous presentation of odor and taste cues followed by a delayed visceral illness leads to a robust aversion towards both conditioned stimuli, which permits diet selection and animal survival. The present experiment was performed in order to investigate the stability or the evolution of the brain network underlying TPOA retrieval during aging. By using immunocytochemical detection of Fos and Egr1 proteins we mapped the cerebral activation induced by TPOA retrieval elicited by the odor presentation in the young, the adult and the senescent rats. The pattern of brain activation changed and the number of activated areas decreased with age. Nevertheless, the piriform cortex and the basolateral amygdala nucleus were always activated and seemed essential for TPOA retrieval. The hippocampus and the neocortical areas could have different implications in TPOA memory in relation to age. The patterns of expression of Fos and Egr1 were different, suggesting their differential involvement in TPOA retrieval. Data are discussed according to the possible roles of the brain areas studied and a model of schematic brain network subtending TPOA retrieval induced by the odor cue is proposed.     

Acute alcohol intoxication paired with appetitive reinforcement: effects upon ethanol intake in infant rats

A recent study suggested that infant rats process alcohol odor and/or taste during acute ethanol intoxication probably due to ethanol elimination via respiration and salivation. The present set of experiments was meant to analyze the possibility that this orosensory processing may act as a conditioned stimulus when an appetitive reinforcer is paired with the state of intoxication. In the first experiment it was observed that intragastric administration of a mildly intoxicating ethanol dose (1.5 g/kg), paired during postabsorptive time intervals with oral infusion of sucrose, was sufficient to promote a significant preference to ethanol. In Experiment 2 different doses of ethanol were either paired or explicitly unpaired with sucrose administration. The result reported in Experiment 1 was replicated and it was observed that a higher dose (3.0 g/kg) unpaired with the reinforcer resulted in alcohol aversions in terms of alcohol consumption patterns. However, when the reinforcer was paired with this dose, the aversion was inhibited. Finally, in the third experiment results indicated that preexposure to alcohol odor eliminates sucrose-conditioned alcohol preferences. These results indicate that, in physiologically immature rats, alcohol preference can be regulated by prior associative experiences involving the state of intoxication and consequences internal and/or inherent to this state.     

Augmentation, not blocking, in an A+/AX+ flavor-conditioning procedure

An A+/AX+ Pavlovian conditioning design typically produces weakened or blocked conditioning to stimulus X. Two experiments were conducted in which rats first received an odor (A+) paired with an emetic US, and then received odor and taste (AX+) paired with the US. In both experiments, the preconditioned odorfacilitated conditioning to the taste. In Experiment 1, a group that received two odor-illness pairings in A+ conditioning had a stronger taste aversion than a group that only had a single odor-illness pairing. Experiment 2 demonstrated that the strengthened taste aversion in the A+/AX+ condition was not due to stimulus generalization. The results represent a unique outcome in the flavor-aversion literature that is similar to potentiation. We propose that this facilitated conditioning to X in the A+/AX+ design be termedaugmentation.     

Conditioned taste and taste-potentiated odor aversions in the Syracuse high- and low-avoidance (SHA/Bru and SLA/Bru) strains of rats (Rattus norvegicus).

Syracuse high- and low-avoidance Long-Evans rats (Rattus norvegicus; SHA/Bru and SLA/Bru) were selectively bred for good and poor active-avoidance learning. However, SLA/Bru animals are superior to SHA/Bru rats in conditioned suppression and passive avoidance learning. In this experiment, saccharin taste and almond odor were the components of a compound conditioned stimulus (flavor) in an illness-induced aversive conditioning paradigm. SLA/Bru rats (n = 17) showed stronger conditioned flavor, taste, and odor aversion than did SHA/Bru animals (n = 18). Unselected Long-Evans rats (n = 18) were intermediate between the selected strains. SLA/Bru and Long-Evans rats showed taste-potentiated odor aversions in this experiment, whereas SHA/Bru animals did not. The results provide evidence that genetic factors, as exemplified by the different strains, are importantly involved in the mechanisms underlying interoceptive and exteroceptive aversive conditioning.     

Simultaneous odor-taste and taste-taste compounds in poison-avoidance learning

In six experiments, rats received an odor or a taste alone or in simultaneous compound with another taste prior to lithium chloride-induced illness. Aversions to the target odor and the target taste were then assessed. In Experiments 1–3, the presence of the taste in compound with the target during conditioning attenuated the strength of the aversions to both the target odor and the target taste. Although these results were consistent with the familiar principles of compound conditioning, they contradicted previous reports of potentiation, rather than attenuation, of odor conditioning by taste. In Experiment 4, taste again attenuated the conditioning of odor when a second odor was presented during the CS-US interval. In Experiment 5, we looked for odor potentiation with a within-subject design, and in Experiment 6, we examined an alternative method of presenting odor. In neither case did we find odor potentiation by taste. Over the range of conditions investigated here, a taste often attenuates, and never potentiates, the conditioning of aversions to both odors and tastes.     

Bilateral lesions of the insular cortex or of the prefrontal cortex block the association between taste and odor in the rat

The neural basis for the association between taste and odor was investigated in the rat. First, behavioral procedures to study the mechanisms underlying the association between qualitative aspects of the odor and taste in rats were developed. Rats were presented with several pairings of the 0.3 mol/L NaCl solution and a flavor, and pairings of distilled water and another flavor. Then the rats received an IP injection of a furosemide to develop sodium deficiency. On the next day, the rats were presented with either of two types of odor-flavored water: water in which the flavor had been paired with NaCl, or water in which the flavor (grape or coffee) had been paired with distilled water. Normal rats avoided ingesting the water flavored with the odor previously paired with NaCl. Sodium-deprived rats, however, ingested the water flavored with that odor. Rats with lesions in either the insular cortex or in the prefrontal cortex neither preferred nor avoided the water flavored with the odor paired with NaCl. It was concluded that rats acquire association between taste and odor, and that the insular and the prefrontal cortices of the rats were involved in this association.     

Extinction and latent inhibition of within-event learning are context specific

Exposure to a solution composed of an odor (almond) and a taste (salt) produced a context-independent preference when rats were subsequently tested with almond under a salt appetite. Postcompound exposure to either the almond or the salt alone reduced almond preferences but only when rats were tested in the extinction context. Exposure to either the almond or the salt in 1 context in advance of exposure to the compound in a different context also reduced preferences but only when the rats were tested in the context in which the element had been pre-exposed. These results show that extinction and latent inhibition of within-event learning are context specific.     

Developmental flavor experience affects utilization of odor, not taste in toxiphobic conditioning

Feeding experiences were varied in developing rats and the effects upon flavor neophobia and lithium chloride-induced flavor aversions were observed. In Experiment 1, nursing experience of neonate rats was reduced by artificial feeding via intragastric cannula; the rats then were tested with apple juice paired with lithium chloride injection at weaning or maturity. Conditioned aversions were not affected, but neophobia to novel apple juice was attenuated in artificially-reared rats tested at maturity. In Experiment 2, rats received enriched feeding experience after weaning, which consisted of (a) obtaining many complex flavors, a few of which were paired with poisoning, effortlessly in the home cage, or (b) foraging for various foods on an elevated maze. No dramatic effects on neophobia or conditioned taste aversion for saccharin water were apparent. In Experiment 3, rats were given experience after weaning with vanilla-scented water either paired or unpaired with quinine water, and then tested with the odor of almond or that odor compounded with saccharin water for neophobia and lithium-induced aversions. Flavor-experienced rats exhibited more pronounced odor conditioning and more resistance to extinction of the odor aversion after both simple and compound conditioning. In contrast, saccharin taste aversions were relatively unchanged. Apparently, enriched feeding and drinking experience facilitates the utilization of odor more than taste cues.     

Potentiation of odor by taste in rats: tests of some nonassociative factors

The contribution of nonassociative neophobia and sensitization to the potentiation of odor by taste in rats was tested in three experiments. In Experiment 1, neophobia for almond odor (O), saccharin taste (T), and odor-taste compound (OT) cues was tested before and after noncontingent lithium chloride poisoning and compared with conditioned aversions produced by OT-LiCl temporal pairing. The OT compound potentiated unconditioned neophobia, but there was no evidence of poison-enhanced neophobia, disinhibition of neophobia, or sensitization by noncontingent LiCl; temporal pairing produced aversions for the compound and its elements. In Experiment 2, generalization to a novel odor was tested after O-LiCl or compound OT-LiCl pairing. The potentiated odor aversion did not generalize to the novel odor; it was specific to the odor paired with taste and LiCl. In Experiment 3, potentiation of the odor component by a discriminant or nondiscriminant taste component was tested. Potentiation was evident only when a novel discriminant taste was in compound with odor prior to LiCl poisoning. These studies support an associative "indexing" hypothesis of the potentiation effect in rats.     

The addition of saccharin to taste cues affects taste preference conditioning in thirsty rats

Previous failures to condition preferences for the unacceptable taste cues sucrose octaacetate (SOA) and citric acid (CA) using a reverse-order, differential conditioning procedure (Forestell & LoLordo, 2000) may have been the result of low consumption of the taste cues in training or of their relatively low acceptability to rats that are thirsty and hungry. In the present study, rats that were thirsty but not hungry readily consumed the SOA and CA conditioned stimulus solutions in training. In test, stronger preferences were displayed for CS+ if the taste cues had been mixed in water (i.e., for the previously unacceptable taste cues) than if they had been made more acceptable by the addition of saccharin in training and test. In Experiment 2, again with rats that were thirsty but not hungry, stronger preferences for CS+ were observed when taste cues were presented in water in the test than when they were presented in saccharin. Addition of saccharin to the taste cues in test eliminated the preference for CS+.     

Taste preconditioning augments odor-aversion learning

On the basis of previous work that has shown a taste can potentiate odor-aversion conditioning in AX+ conditioning, 6 experiments used rats to examine the effects of pairing a preconditioned taste (A) with a novel odor cue (X) in an A+/AX+ aversion conditioning design. Experiments 1A and 1B demonstrated that a preconditioned taste produced a robust odor aversion that was significantly stronger than a potentiated odor aversion. The results of Experiment 2 showed that the robust odor aversion produced by A+/AX+ conditioning was not the result of the potentiated odor aversion summating with generalization from the taste aversion. The augmented odor aversion was produced only when the taste and odor stimuli were presented simultaneously (Experiment 3) and the preconditioned taste aversion was intact at compound conditioning (Experiment 4). Pairing a novel odor with a preconditioned taste was not sufficient to condition an aversion to odor (Experiment 5), although other results implicated a role for an association between odor and taste in the odor augmentation effect (Experiment 6). The present results have implications for current models of taste + odor interactions in flavor-aversion conditioning.     

条件性味觉厌恶分化后臂旁核c-fos表达的变

以口内注入糖精或蔗糖溶液为条件刺激,腹腔内注射LiCl为非条件刺激,在大鼠形成条件性味觉厌恶后进行分化训练,观察味质和嗜好性对臂旁核各亚核c-fos表达的影响及其交互作用。结果表明：味质和嗜好性对背侧外侧亚核(dls)和腹侧外侧亚核(vls)的c-fos表达无影响;在内侧外侧亚核(ils)和外部内侧亚核(ems),蔗糖诱导的c-fos表达高于糖精,但在外部外侧亚核(els),糖精诱导的表达高于蔗糖;嗜好性刺激引起ils、中央外侧亚核(cls)和cms内c-fos高表达,厌恶性刺激引起ems和els内的高表达。在ils和cms嗜好性与味质的影响各自独立,在els和ems内嗜好性与味质的影响存在交互作用。提示PBN内存在味质辨别和报酬评价的代表区,两种代表区有交迭,ems和els对味质信息和报酬信息的整合有重要作用     

The effects of prenatal stress on motivation in the rat pup

Exposure to prenatal stress (PNS) has been shown to induce a set of psychological and behavioral changes in developing offspring. We used the rodent model to investigate whether PNS produces changes in the ability of the pup to express social motivation. We used a set of behavioral tasks including monitoring ultrasonic vocalizations after isolation, a conditioned place preference, and a novel and familiar odor approach test. Pregnant Long-Evans rats were exposed to an unpredictable, variable stressor twice daily during the third week of gestation. Isolation vocalizations were assessed on postnatal day (PND) 10. Pup affinity for the dam was evaluated on PND 15. Typically, pups display a selective preference for an odor-paired environment only after the odor has been associated with the dam. This previous association produces a positive conditioned stimulus (CS). Normally, pups exposed to a neutral CS (odor paired with cotton balls) do not form this place preference. Results indicate that PNS exposed pups had significantly increased distress vocalizations and an equal preference for the positive and neutral conditioned stimuli. This type of alteration in forming early preferences could be detrimental because of decreases in the specificity of social learning and an impaired responsiveness in social relationships.     

Inactivation of the basolateral amygdala impairs the retrieval of recent and remote taste-potentiated odor aversion memory

Memory reorganization as a time-dependent process can be investigated using various learning tasks such as the taste-potentiated odor aversion (TPOA). In this paradigm rats acquire a strong aversion to an olfactory cue presented simultaneously with a gustatory cue. Together these cues are paired with a delayed visceral illness. The basolateral amygdaloid nucleus (BLA) plays a key role in TPOA acquisition but its involvement in retrieval remains unclear. We investigated the involvement of the BLA in either recent or remote retrieval of TPOA. In each case, the number of licks observed in response to the presentation of either the odor or the taste was used to assess retrieval. Before the retrieval test, rats received a bilateral infusion of lidocaine to inactivate the BLA. We observed that both recent and remote TPOA retrieval tests induced by the odor presentation were disrupted in the lidocaine-injected rats. By contrast, the BLA inactivation had no effect upon the aversion towards the taste cue regardless of the time of retrieval. The present study provides evidence that BLA functioning is necessary for retrieval of aversive odor memory, even with a long post-acquisition delay.     

Negative anticipatory contrast and preference conditioning: flavor cues support preference conditioning, and environmental cues support contrast.

In 2 experiments, access to a 0.15% saccharin solution was followed on alternating days by access to a 32% sucrose solution and the same saccharin solution. In Experiment 1, rats increased both intake of and preference for a flavored saccharin solution that predicted sucrose, but neither effect was found using a predictive odor cue alone. Experiment 2 replicated the predictive flavor results but showed suppression of saccharin intake when environmental cues predicted sucrose. When both flavor and environment predicted sucrose, saccharin intake did not change, but preference for the predictive flavor increased. Discriminative taste cues appear to facilitate the development of preference conditioning, but environmental cues favor negative anticipatory contrast effects. Also, preference conditioning and contrast may develop concurrently and compete for expression.     

Behavioral modulation induced by food odor aversive conditioning and its influence on the olfactory responses of an oscillatory brain network in the slug Limax marginatus

We compared behaviorally and physiologically the olfactory responses of slugs (Limax marginatus) that had been subjected to aversive, appetitive, or unpaired training with food odors (carrot or cucumber). In the aversive training, the slugs were exposed to the food odor as a conditioned stimulus (CS), and then quinidine sulfate solution as an unconditioned stimulus (UCS) was immediately applied to the lip of the slugs. This training caused a decrease in preference level for the CS. The unpaired training, in which the CS and the UCS were presented to the slugs with a 5-min interval, induced no change in the preference level for the CS. In the appetitive training, the slugs were allowed to eat the CS odor source without UCS application. When we used nonstarved slugs, it was found that the preference level for the CS increased upon the appetitive training. These results indicate that each training changed the preference for the odors in a characteristic manner. In the physiological experiments, we used brain-inferior tentacular nose preparations isolated from slugs and investigated the olfactory responses of the oscillations in the local field potential (LFP) of the procerebral (PC) lobe. We found that odor presentation induced various types of changes in the LFP oscillation frequency, although the rate of occurrence of the frequency modulation differed between odors used in the aversive and the unpaired training (aversive-conditioned and unpaired odors). The aversive-conditioned odors induced a decrease in the oscillatory frequency. Unpaired odors did not change it. Moreover, odors used in the appetitive training (appetitive-conditioned odors) induced an increase in the frequency. Thus, it was considered that those modulations of PC lobe oscillatory activity were independent of odor and reflected learned preference for odors.     

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.