Taste Neophobia Research Articles

Taste Neophobia, Latent Inhibition of Taste Aversion and Object Recognition Memory in Adolescent Rats.

Adolescence in mammals is a period marked by increased novelty-seeking and enhanced responsiveness to the stressful properties of novel stimuli. Despite the need to taste potentially toxic novel foods during the adolescent growth spurt, there has been little study of taste neophobia and its attenuation. Four experiments were carried out to compare taste neophobia and related memory processes in male and female adolescent (PND28) and adult (PND70) Wistar rats. Experiments 1 and 2 evaluated attenuation of taste neophobia to cider vinegar (3%) and sodium saccharin (0.1%) solutions were evaluated. Additionally, to test the role of memory in neophobia during adolescence, latent inhibition of taste aversion and object recognition memory were assessed in Experiment 3 and Experiment 4, respectively. Adolescent and adult rats exhibited taste neophobia to the saccharin solution but adolescent rats required more exposure trials than adults to recognize the vinegar solution as safe. Both groups exhibited similar latent inhibition of taste aversion and object recognition memory. No sex effect was significant. Contrary to the accepted view associating adolescence with reduced neophobia, adolescent rats exhibited taste neophobia which even increased when sour tastes were encountered.

Increased basolateral amygdala metabolic activity during flavor familiarization: an experimental study

BackgroundNovel flavors elicit a cautious neophobic response which is attenuated as the flavor becomes familiar and safe. The attenuation of neophobia reveals the formation of a safe memory. Previous lesion studies in rats have reported that basolateral amygdala integrity is required for taste neophobia, but not neophobia to flavor, i.e., taste linked to an odorous component. Accordingly, immunohistochemical analyses show that novel tastes induced higher basolateral amygdala activity when compared to familiar ones. However, a different role of basolateral amygdala in flavor attenuation of neophobia is suggested by lesion studies using a vinegar solution. Studies assessing basolateral amygdala activity during flavor attenuation of neophobia are lacking. Thus, we quantified cytochrome oxidase as an index of basolateral amygdala activity along the first and second vinegar exposures in order to assess flavor neophobia and attenuation of neophobia.MethodsWe exposed adult male Wistar rats either once or twice to a 3% cider vinegar solution or water, and compared the basolateral amygdala, piriform cortex and caudate putamen brain metabolic activity using cytochrome c-oxidase histochemistry.ResultsWe found increased flavor intake and cytochrome c-oxidase histochemistry activity during the second exposure in basolateral amygdala, but not in the piriform cortex and caudate/putamen.ConclusionsThe main finding of the study is that BLA metabolic activity was higher in the group exposed to a familiar vinegar solution than in the groups exposed to either water or a novel vinegar solution.

Expression of c-Fos following voluntary ingestion of a novel or familiar taste in rats

Taste neophobia, the rejection of novel tastes or foods, involves an interplay of various brain regions encompassing areas within the central gustatory system, as well as nuclei serving other functions. Previous findings, utilising c-Fos imaging, identified several brain regions which displayed higher activity after ingestion of a novel taste as compared to a familiar taste. The present study extends this analysis to include additional regions suspected of contributing to the neurocircuitry involved in evoking taste neophobia. Our data show increased c-Fos expression in the basolateral amygdala, central nucleus of the amygdala, gustatory portion of the thalamus, gustatory portion of the insular cortex and the medial and lateral regions of the parabrachial nucleus. These results confirm the contribution of areas previously identified as active during ingestion of novel tastes and expose additional areas that express elevated levels of c-Fos under these conditions, thus adding to the neural network involved in the detection and initial processing of taste novelty.

Insula to mPFC reciprocal connectivity differentially underlies novel taste neophobic response and learning in mice.

To survive in an ever-changing environment, animals must detect and learn salient information. The anterior insular cortex (aIC) and medial prefrontal cortex (mPFC) are heavily implicated in salience and novelty processing, and specifically, the processing of taste sensory information. Here, we examined the role of aIC-mPFC reciprocal connectivity in novel taste neophobia and memory formation, in mice. Using pERK and neuronal intrinsic properties as markers for neuronal activation, and retrograde AAV (rAAV) constructs for connectivity, we demonstrate a correlation between aIC-mPFC activity and novel taste experience. Furthermore, by expressing inhibitory chemogenetic receptors in these projections, we show that aIC-to-mPFC activity is necessary for both taste neophobia and its attenuation. However, activity within mPFC-to-aIC projections is essential only for the neophobic reaction but not for the learning process. These results provide an insight into the cortical circuitry needed to detect, react to- and learn salient stimuli, a process critically involved in psychiatric disorders.

Effect of hippocampal 6-OHDA lesions on the contextual modulation of taste recognition memory

Taste recognition memory is evident in rodents because the initial neophobia to novel tastes attenuates across exposures as the taste becomes familiar and safe. This attenuation of taste neophobia (AN) is context-dependent and an auditory background change could induce the recovery of the neophobic response. The AN auditory context-dependency requires the hippocampal integrity but the neurochemical mechanisms underlying the interaction with the taste memory circuit remain unexplored. We have applied pharmacological intervention by 6-hidroxydopamine (6-OHDA) hippocampal lesion for assessing the role of catecholamines in the hippocampal system to Wistar rats that drank a novel 3% vinegar solution for several consecutive days. Additionally, we manipulated the auditory background as a context that could either change or remain constant across all the drinking sessions. We found that a disruption of the context-dependent AN was induced by intracerebral administration of 6-OHDA targeted to the ventral CA1 hippocampus (vCA1). We conclude that the ability of the auditory context to modulate taste recognition memory involves the catecholaminergic activity in the ventral hippocampal circuit for the proper acquisition of safe taste memory.

Disconnection of the perirhinal and insular cortices severely disrupts taste neophobia

It is well known that the perirhinal (Prh) and insular (IC) cortices are reciprocally connected, mainly through ipsilateral projections. Although some studies have demonstrated that excitotoxic lesions to these regions, each separately, disrupt taste neophobia, it is not yet known whether the two regions have functional interactions with one another. To find out if they form a functional unit, we examined the effects of crossed excitotoxic lesions to the Prh and the contralateral IC (contralateral group). This group's performance was compared to that of rats with ipsilateral Prh and IC lesions (ipsilateral group) and to that of control-operated rats. All the animals received a 0.3% saccharin solution for fifteen minutes on five consecutive days. Rats with contralateral Prh-IC lesions drank significantly higher amounts of saccharin than the other groups during the first encounter with the novel taste, indicating a disruption in neophobia. However, the lesions did not disrupt attenuation of neophobia, with the contralateral group reaching asymptote in trial 2 and the rest of the groups after 3–5 days of exposure to the saccharin. These findings suggest that both Prh and IC play a necessary role in taste neophobia. Additionally, the two cortices function interdependently and their interaction is critical for normal expression of taste neophobia.

Accumbens and amygdala in taste recognition memory: The role of d1 dopamine receptors

The attenuation of taste neophobia (AN) is a good model for studying the structural and neurochemical mechanisms of the emotional component of memory because taste recognition memory exhibits the unique feature of being necessarily linked to hedonic properties. Whilst novel tastes elicit cautious neophobic responses, taste exposures which are not followed by aversive consequences attenuate neophobia as the taste becomes safe and palatable. Given the involvement of the nucleus accumbens in reward and of the amygdala in emotional memories, we applied c-Fos immunohistochemistry as an index of neural activity in Wistar rats that were exposed to a vinegar solution for one, two or six days. An inverse pattern of accumbens nucleus vs amygdala activity was found on the second exposure day on which AN occurred. The number of c-Fos positive cells in the nucleus accumbens shell increased whilst the number of c-Fos positive cells in the basolateral amygdala decreased. Further analyses revealed a positive correlation between AN and the number of c-Fos positive cells in the accumbens shell but a negative correlation in the basolateral amygdala. Furthermore the accumbens-amygdala interplay relevant for AN seems to be mediated by dopamine D1 receptors (D1DR). The injection of SCH23390 (D1DR antagonist) in both the accumbens shell and the basolateral amygdala on the second taste exposure resulted in selectively impaired AN but had opposite long term effects. This finding supports the relevance of a dopaminergic network mediated by D1DRs in the nucleus accumbens shell and basolateral amygdala which is critical for adding the emotional component during the formation of taste memory.

Perirhinal cortex supports both taste neophobia and its attenuation

Rats are often reluctant to consume novel tastes because they lack knowledge about the postingestive effects the new foods might have. This paper examines the effect of excitotoxic lesions and temporary inactivation of the perirhinal cortex (Prh), a key region in the recognition memory system, on taste neophobia and its attenuation. Using a two-bottle choice paradigm (saccharin vs water), excitotoxic lesions were found to disrupt taste neophobia to 0.3% and 0.5% saccharin. However, the lesions had no effect when using a concentration of 0.7%, which is qualitatively aversive (expt. 1a-1c). In a second series of experiments the same animals were able to acquire a flavor preference learning on the basis of a flavor-taste association. Lesioned and control rats showed, during a choice test, a clear preference for the flavor associated with saccharin (expt. 2a-2c). Finally, in a third series of experiments, Prh inactivation with lidocaine after trial 1 (expt. 3) and after trials 1-3 (expt. 4) delayed attenuation of the neophobia. These findings suggest that Prh lesions do not significantly affect taste processing/ perception. Prh thus appears to play an essential role in taste neophobia and its attenuation.

Prefrontal cortex activity patterns during taste neophobia habituation in adult and aged rats

Age-related memory decline has been associated with changes in the medial prefrontal cortex (mPFC) function. In order to explore the role of mPFC in taste recognition memory, we have assessed mPFC c-Fos immunoreactivity in adult (5-month-old) and aged (24-month-old) male Wistar rats during the first (Novel), second (Familiar I), and sixth (Familiar II) exposure to a cider vinegar solution. Adult brains showed higher c-Fos expression in the ventral but not the dorsal region of mPFC during the second taste exposure. Interestingly, old brains exhibited an altered activity pattern selectively in the dorsal peduncular cortex (DP) which can be associated with a delayed attenuation of vinegar neophobia in this group. These results support the involvement of this area in the formation of safe taste memory. Further research is needed for understanding the role of DP in taste recognition memory and the impact of aging on it.

The effects of novelty on food consumption in male and female rats

Novelty powerfully impacts feeding behavior and can override homeostatic and hedonic drives, because consumption of a new food could lead to illness or even death. New foods and new feeding environments can decrease or inhibit feeding, but how the two interact and whether there are sex differences has not been determined. The current study examined consumption of a palatable (high sucrose) novel food compared to a familiar food in adult male and female rats that were fed in a familiar or a novel environment. Rats were deprived of food for 20 h prior to each of eight tests. During the first test, male and female rats that were tested in a familiar environment showed robust taste neophobia, as they mainly consumed familiar food. Across repeated tests, these rats increased consumption of the novel food, which indicated that they habituated to the novel taste and developed a preference for the novel food. In contrast, all rats tested in a novel feeding environment ate very little of both foods during the initial test. Across repeated tests, male rats habituated to the novel food faster than females and by the fourth test ate more of the novel than familiar food. In contrast, females showed sustained, suppressed consumption across habituation tests. These results demonstrated robust differences in feeding behavior depending whether rats were fed at home or in a novel feeding environment, and robust sex differences in habituation to eating in a new environment. These findings suggest that novel context has a greater impact on female consumption than male consumption. This difference may be relevant to sex differences in avoidant behaviors in maladaptive circumstances and the development of psychopathology. Therefore, the behavioral profile outlined in this study for consumption under novelty provides an important starting point for investigation of the underlying neural substrates of novelty processing.

The auditory context-dependent attenuation of taste neophobia depends on D1 dopamine receptor activity in mice

Taste recognition memory in rodents is evident as taste neophobia disappears upon repeated taste exposures without aversive consequences, thus increasing the consumption of familiar edibles. The attenuation of taste neophobia (AN) induced by taste familiarity is auditory context-dependent in mice since neophobia to a familiar taste reappears with a novel auditory background. This effect depends on the integrity of the dorsal hippocampus but the potential role of dopamine has remained unexplored. In order to explore the involvement of dopamine through D1 dopamine receptors in AN, C57BL/6 mice were exposed to a 3% vinegar taste solution for 10 min throughout several consecutive days. An experimentally-controlled auditory background was used to define a context, which could either change or remain constant throughout all the drinking sessions. Systemic administration of the D1 dopamine receptor antagonist SCH-23390 induced a similar effect to that of an auditory context change while it was kept constant and systemic administration of SKF-81297 prevented the contextual modulation of AN when the auditory context changed. Additionally, SCH-23390 injection on the following day to the auditory context change further impaired AN, thus suggesting the relevance of dopamine in the consolidation of the context dependency of taste recognition memory. We conclude that the context dependency of the AN involves dopaminergic activity mediated by D1 receptors which might be responsible for proper acquisition of safe taste recognition memory.

Inactivation of the basolateral amygdala suppresses the expression of taste neophobia but not the retrieval process in attenuation of neophobia

Taste neophobia is a behavior seen in rodents that involves reduction in the consumption of a novel food or drink. In the absence of negative post-ingestive consequences, consumption increases with exposure. In this study, we examined the effect of pharmacological inactivation of the basolateral nucleus of the amygdala (BLA) on taste neophobia in rats using muscimol, a GABAA receptor agonist. Rats treated with muscimol infused into the bilateral BLA showed a suppressed but not totally abolished neophobic reaction to a novel saccharin solution compared to that observed in control rats. This result indicates that BLA function is important, but not essential, for expression of a neophobic reaction to a novel sweet taste solution. However, infusion of muscimol into the BLA did not disrupt attenuation of neophobia, which implies the presence of a retrieval process in safe taste memory.

Dorsal hippocampal damage disrupts the auditory context-dependent attenuation of taste neophobia in mice.

Rodents exhibit neophobia for novel tastes, demonstrated by an initial reluctance to drink novel-tasting, potentially-aversive solutions. Taste neophobia attenuates across days if the solution is not aversive, demonstrated by increased consumption as the solution becomes familiar. This attenuation of taste neophobia is context dependent, which has been demonstrated by maintained reluctance to drink the novel tasting solution if the subject has to drink it after being brought to a novel environment. This spatial context-dependent attenuation of taste neophobia has been described and likely depends on the integrity of the dorsal hippocampus because this brain area is crucial for representing space and spatial context associations, but is unnecessary for processing taste memories per se. Whether changing the non-spatial auditory context causes a similar effect on attenuation of taste neophobia and the potential role of the dorsal hippocampus in processing this decidedly non-spatial information has not been determined. Here we demonstrate that changing the non-spatial auditory context affects the attenuation of taste neophobia in mice, and investigate the consequence of hippocampal lesion. The results demonstrate that the non-spatial auditory context-dependent attenuation of taste neophobia in mice is lost following NMDA excitotoxic lesions of the CA1 region of the dorsal hippocampus. These findings demonstrate that the dorsal hippocampus is crucial for the modulation non-associative taste learning by auditory context, neither of which provide information about space.

Inhibiting gustatory thalamus or medial amygdala has opposing effects on taste neophobia.

Taste neophobia is a feeding system defense mechanism that limits consumption of an unknown, and therefore potentially dangerous, edible until the post-ingestive consequences are experienced. We found that transient pharmacological inhibition (induced with the GABA agonists baclofen and muscimol) of the gustatory thalamus (GT; Experiment 1), but not medial amygdala (MeA; Experiment 2), during exposure to a novel saccharin solution attenuated taste neophobia. In Experiment 3 we found that inhibition of MeA neurons (induced with the chemogenetic receptor hM4DGi) enhanced the expression of taste neophobia whereas excitation of MeA neurons (with hM3DGq) had no influence of taste neophobia. Overall, these results refine the temporal involvement of the GT in the occurrence of taste neophobia and support the hypothesis that neuronal excitation in the GT is necessary for taste neophobia. Conversely, we show that chemogenetically, but not pharmacologically, inhibiting MeA neurons is sufficient to exaggerate the expression of taste neophobia.

The effects of amygdala and cortical inactivation on taste neophobia.

The current study examined the effects of transient inactivation of the basolateral amygdala (BLA; Experiment 1) and gustatory cortex (GC; Experiment 2) on the expression of taste neophobia and its recovery. We found that inactivation (induced by infusions of baclofen/muscimol) of each structure before exposure to a novel saccharin (0.5%) solution elevated intake on Trial 1 (i.e., taste neophobia was attenuated) and, surprisingly, decreased intake on Trial 2. It seems unlikely that this intake reduction on Trial 2 can be attributed to taste aversion learning caused by drug infusions because in the subsequent experiments with the same set of the implanted animals, the rats did not decrease intake when baclofen/muscimol was infused after taste presentation on Trial 1. The latter result suggests that BLA or GC inactivation that attenuates taste neophobia may also impair memory consolidation of a safe taste experience.

Effects of extensive amygdaloid lesions on conditioned taste aversion in rats

The role of the amygdala in the acquisition of conditioned taste aversion (CTA) is unclear. The lesion studies that have explored specific nuclei of the amygdala point to a probable involvement of the basolateral amygdala, but it remains unclear whether the function of the amygdala in CTA is limited to the activity of the basolateral amygdala. In the current study, extensive bilateral lesions of the amygdala were performed in Wistar rats to explore if the destruction of the amygdala affects the acquisition of CTA, as has been reported with selective lesions of the basolateral amygdala. The magnitude of the taste aversion of animals with extensive lesions of the amygdala was compared with those of animals with similar lesions of the striatum (a structure apparently unrelated to CTA) and animals without lesions. Taste aversion was analyzed by the one‑bottle test and two‑bottle choice test. The results of the one‑bottle test indicated that amygdaloid lesions significantly reduced the magnitude of taste aversion compared with that of animals without lesions. Animals with lesions of the amygdala also showed a greater preference for the conditioned taste stimulus, but this preference did not reach statistical significance. Besides the effect on CTA, animals with amygdaloid lesions showed no evidence of taste neophobia on the day of conditioning. These findings suggest that amygdaloid lesions may affect CTA by disrupting the perception of novelty during conditioning in a manner similar to the effect reported with basolateral lesions.

Complex effects of reward upshift on consummatory behavior

Exposing rats to an upshift from a small reward to a larger reward sometimes yields evidence of consummatory successive positive contrast (cSPC), an effect that could be a suitable animal model of positive emotion. However, cSPC is an unreliable effect. Ten experiments explored the effects of an upshift in sucrose or saccharin concentration on consummatory behavior under several conditions. There was occasional evidence of cSPC, but mostly a combination of increased consummatory behavior relative to preshift reward concentrations and a reduced behavioral level relative to unshifted controls. Such a pattern is consistent with processes causing opposite changes on behavior. Reward upshift may induce processes that suppress behavior, such as taste neophobia (induced by an intense sucrose taste) and generalization decrement (induced by novelty in reward conditions after the upshift). An experiment tested the role of such novelty-related effects by preexposing animals to either the upshift concentration (12% sucrose) or water during three days before the start of the experiment. Sucrose-preexposed animals drank significantly more than water-preexposed animals during the upshift, but just as much as unshifted controls (i.e., no evidence of cSPC). These results suggest that cSPC may be difficult to obtain reliably because reward upshift induces opposing processes. However, they also seriously question the ontological status of cSPC.

Latent inhibition of conditioned taste aversion in rats with amygdaloid or hippocampal lesions

The amygdala and hippocampus play crucial roles in the latent inhibition of different conditioned responses, such as fear conditioned. Nevertheless, the involvement of these structures in the latent inhibition of conditioned taste aversion (CTA) is uncertain. In the present study, we explore the relevance of the amygdala and hippocampus in latent inhibition using a CTA paradigm. The effects of taste pre-exposures vs. non-pre-exposures on taste aversion conditioning were compared in Wistar rats with amygdaloid or hippocampal excitotoxic lesions. All pre-exposed animals consumed significantly more on the test day than did non-pre-exposed animals. Therefore, neither amygdaloid nor hippocampal lesions prevented the latent inhibition phenomenon. However, the expected taste neophobia was potentially affected by lesions to either the amygdala or hippocampus. These findings suggest that the amygdala and hippocampus seem to be necessary for taste neophobia but not for the acquisition of latent inhibition of CTA. The differential involvement of both structures in latent inhibition under different associative learning paradigms is briefly discussed.

Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia.

Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF) mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA) dependent activity changes in the perirhinal cortex (PRh) during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naïve male Wistar rats were exposed to a saccharin solution (0.4%) during the first (novel), the second (Familiar I), and the sixth presentation (Familiar II). Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR) using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function.

Differential contribution of perirhinal cortex and hippocampus to taste neophobia: Effect of neurotoxic lesions

Although the perirhinal cortex (Prh) has been extensively related to recognition memory, little is known about its specific role in taste memories. The main aim of the present series was therefore to examine the effect of neurotoxic lesions of the Prh on taste neophobia, a phenomenon consisting of a low intake of a novel food until its postingestive consequences are determined. The results showed that Prh-lesioned rats consumed significantly more novel saccharin in trial 1 than control subjects when a saccharin solution of 0.3% (expt. 1a) and 0.5% (expt. 1b) was presented. However, when the saccharin concentration was high and qualitatively more aversive, Prh lesions did not affect the neophobic response (0.7%, expt. 1c) and the lesioned and control animals consumed a similar amount of the fluid during the first and subsequent test trials. In all three experiments, Prh-lesioned and control rats showed a comparable intake at asymptote. Experiment 2 and 3 showed that neurotoxic lesions to the dorsal hippocampus prior to or 24h after the intake of the novel taste (0.3% saccharin) had no effect on the initial occurrence of the neophobic response or on the consolidation of safe taste memory, respectively. These findings support a dissociation of functions between the Prh and the hippocampus in taste neophobia. Also, the data suggests that the Prh plays an essential role in detecting the novelty of the new tastant.