Saccharin Taste Research Articles

Conditioned nausea induced by cisplatin and emetine identified by a taste reactivity test in rats

No prior studies have shown that gaping reactions are produced with the avoidance of conditioned taste caused by cisplatin and emetine. Therefore, we tried to demonstrate it using a taste reactivity test in rats and found the gaping reactions induced when saccharin is readministered after gustatory conditioning that paired saccharin with cisplatin or emetine. Since conditioned gaping reactions indicate the aversion to saccharin taste and conditioned nausea, the present study suggest that the taste aversion is induced by cisplatin and emetine. It was also found that with intraperitoneal injections of emetine alone, gaping almost never occurs.

Taste-Associative Learning in Rats: Conditioned Immunosuppression with Cyclosporine A to Study the Neuro-Immune Network.

The pharmacological effects of an immunosuppressive drug, such as cyclosporine A (CsA), can be learned and retrieved by humans and animals when applying associative learning paradigms. This principle is based on Pavlovian conditioning, in which repeated presentation of an "unconditioned stimulus" (US; here, the drug CsA) is paired with exposure to a "conditioned stimulus" (CS; here, the novel taste of saccharin). Re-exposure to the CS at a later time leads to an avoidance behavior. Concomitantly, using this paradigm, animals exposed to the CS (saccharin) display immunosuppression, reflected by reduced splenic T-cell proliferation and diminished interleukin-2 and interferon-γ expression and release in ex vivo cultured splenocytes, mimicking the pharmacological effects of the US (CsA). Notably, this paradigm of taste-immune associative learning demonstrates the impressive abilities of the brain to detect and store information about an organism's immunological status and to retrieve this information, thereby modulating immunological functions via endogenous pathways. Moreover, conditioned pharmacological effects, obtained by means of associative learning, have been successfully implemented as controlled drug-dose reduction strategies as a supportive treatment option to optimize pharmacological treatment effects for patients' benefit. However, our knowledge about the underlying neurobiological and immunological mechanisms mediating such learned immunomodulatory effects is still limited. A reliable animal model of taste-immune associative learning can provide novel insights into peripheral and central nervous processes. In this article, we describe protocols that focus on the basic taste-immune associative learning paradigm with CsA and saccharin in rats, where conditioned peripheral immunosuppression is determined in ex vivo cultured splenocytes. The behavioral protocol is reliable and adaptable and may pave the road for future studies using taste-immune associative learning paradigms to gain deeper insight into brain-to-immune-system communication. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Taste-immune associative learning with cyclosporine A Basic Protocol 2: Splenocyte isolation and cultivation to study stimulation-induced cytokine production.

927 Efficacy of Surgical Helmet Systems for Protection Against COVID-19: A Double-Blinded Randomised Control Study

IntroductionThis study assesses whether sterile surgical helmet systems (SSHS) provide additional protection from aerosol pathogens alongside protecting against splash. There has been debate on whether to use such systems in orthopaedic surgery during the COVID-19 pandemic.MethodThirty-five participants were enrolled in a double-blinded randomised controlled study investigating efficacy of the Stryker Flyte Surgical Helmet (Stryker Corporation, Kalamazoo, MI, USA) as protection against respiratory droplets. Wearing the SSHS in a fit testing hood, subjects were randomised to nebulised saccharin solution or placebo. Twenty were allocated to the saccharin group with 15 to placebo. Positive sweet taste represented test failure. Taste tests were performed with the helmet fan turned on and off.ResultsSSHS did not prevent saccharin taste (p < 0.0001). Within the saccharin cohort, 40% recorded a positive taste with the fan on and 100% with the fan off. There was a statistically significant difference in mean time-to-taste saccharin (p = 0.049) comparing fan on (123.5 s) vs. off (62.6 s).ConclusionsSSHS do not protect against aerosol particulate and therefore are not efficacious in protection against COVID-19. The fan system employed may even increase risk by drawing in particulates and delaying recognition of intraoperative cues that point to respirator mask leak.

Efficacy of surgical helmet systems for protection against COVID-19: a double-blinded randomised control study.

PurposeThis study assesses whether sterile surgical helmet systems (SSHS) provide surgeons with additional protection from aerosol pathogens alongside their traditional role protecting against splash. There has been debate on whether to use such systems in reopening elective orthopaedic surgery during the current COVID-19 pandemic environment.MethodsThirty-five participants were enrolled in a double-blinded randomised controlled study investigating efficacy of the Stryker Flyte Surgical Helmet (Stryker Corporation, Kalamazoo, MI, USA) as protection against respiratory droplets. Wearing the SSHS in a fit testing hood, subjects were randomised to nebulised saccharin solution or placebo. Twenty were allocated to the saccharin group with 15 to placebo. Positive sweet taste represented a failure of the test. Taste tests were performed with the helmet fan turned on and off.ResultsSSHS did not prevent saccharin taste (p < 0.0001). Within the saccharin cohort, 40% recorded a positive taste with the fan on and 100% with the fan off. There was a statistically significant difference in mean time-to-taste saccharin (p = 0.049) comparing fan on (123.5 s) vs. off (62.6 s).ConclusionsSSHS do not protect against aerosol particulate and therefore are not efficacious in protection against COVID-19. The fan system employed may even increase risk to the surgeon by drawing in particulates as well as delay recognition of intraoperative cues, such as exhaust from diathermy, that point to respirator mask leak.

Evaluation of nasal mucociliary clearance time in children with celiac disease

ObjectivesCeliac disease is an autoimmune disorder that develops because of sensitivity to gluten-containing grains in genetically disposed individuals. Nasal mucociliary clearance is the most important protective factor that protects the upper and lower airways from foreign particulates. This study aimed to investigate the effect of celiac disease on nasal mucociliary clearance. MethodsThe study included patients with celiac disease and healthy children. Nasal mucociliary clearance time was measured using the saccharin test. The children's saccharin taste time was recorded in seconds. ResultsOverall, 65 children were included: 43 patients with celiac disease (66.2%) and 22 healthy children (33.8%). Of all the children, 42 (64.6%) were female, and the average age was 11.8 ± 4 years. Nasal mucociliary clearance time of patients with celiac disease (531 ± 155 s) was significantly prolonged in comparison to that of healthy children (448 ± 80 s) (p = 0.006). No relationships were found between the diagnosis age, celiac type, and histopathological phase and compliance with the gluten-free diet and nasal mucociliary clearance time of patients with celiac disease. ConclusionsThis study showed that nasal mucociliary clearance was prolonged in patients with celiac disease. A defect in nasal mucociliary clearance increases the risk of infection and inflammation in small airways. Studies reported a high prevalence of respiratory tract infection in patients with celiac disease, which was associated with malnutrition, vitamin deficiency, and hyposplenism. The findings of the present study indicated that impairment of nasal mucociliary clearance could play a role in the development of frequent lung infections in patients with celiac disease.

Behaviorally conditioned immunosuppression with cyclosporine A forms long lasting memory trace

Behaviorally conditioned taste avoidance (CTA) paradigms using the novel taste saccharin as a conditioned stimulus (CS) and the immunosuppressive drug cyclosporine A (CsA) as unconditioned stimulus (US) demonstrate learned suppression of immune functions. However, conditioned immune responses might decrease over time depending on the period between acquisition and retrieval (retention interval). Thus, the present study investigated whether and to what extent prolonged 14- and 30-days retention intervals affect conditioned behavioral (CTA) and immune responses in rats. Our findings demonstrate that conditioned animals displayed a marked CTA after 14 and 30 days upon CS re-exposure compared to control animals. More importantly, the production of the pro-inflammatory cytokine interferon (IFN)-γ was significantly suppressed in ex vivo anti-CD3 stimulated splenocytes of conditioned animals compared to controls at both time points. These findings document that CTA paradigms using the immunosuppressive drug CsA as US form long lasting memory traces of the learned behavioral and immune responses.

Behavioral Responses of Chicks to a Saccharin-Quinine Mixture.

To date, few reports have been published on the sensitivity of birds to sweet tastes. Therefore, in this study, the behavioral responses of White Leghorn chicks to the sweet taste of saccharin and the bitter taste of quinine were assessed. Three chicks were provided with a solution of 3.0 mM quinine and a mixture of 3.0 mM quinine mixed with 0.1, 0.5, 1.0, or 10.0 mM saccharin in a two-bottle choice test for 48 h. It was found that the chicks consumed more of the 0.5 mM saccharin/3.0 mM quinine mixture but significantly less of the 10.0 mM saccharin/3.0 mM quinine mixtures than the quinine solution alone (P<0.05). The aversive behavior of 3.0 mM quinine solution was eased when mixed with 0.5 mM saccharin, indicating that chicks are detecting the sweetness associated with the 0.5 mM saccharin. The aversion to the 1.0 and 10.0 mM saccharin solutions might be stronger than to the 3.0 mM quinine solution alone. These findings suggest that chicks are able to detect this artificial sweetener.

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5gkg-1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press-evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham- and LHb-lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol-induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake.

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats.

Cocaine decreases saccharin preference without altering sweet taste sensitivity

In rodents, saccharin consumption is suppressed when the sweet taste stimulus is paired with moderate doses of cocaine. Several hypotheses have been used to explain the seemingly contradictory effect of decreased consumption of a normally preferred substance following a highly rewarding drug. A common theme across these hypotheses is that saccharin is interpreted as less rewarding after cocaine pairing. We considered the alternative possibility that suppression is caused not by a change in reward circuitry, but rather by a change in taste detection, for instance by altering the afferent taste response and decreasing sensitivity to sweet taste stimuli. To evaluate this possibility, we measured saccharin taste sensitivity of mice before and after a standard cocaine-pairing paradigm. We measured taste sensitivity using a brief-access lickometer equipped with multiple concentrations of saccharin solution and established concentration–response curves before and after saccharin–cocaine pairing. Our results indicate that the EC50 for saccharin was unaltered following pairing. Instead, the avidity of licking saccharin, an indicator of motivation, was depressed. Latency to first-lick, a negative indicator of motivation, was also dramatically increased. Thus, our findings are consistent with the interpretation that saccharin–cocaine pairing results in devaluing of the sweet taste reward.

Effect of Gender on Nasal Mucociliary Clearance

Background: The sexual dimorphism favours gender specific biological characteristics influenced by sex hormones. These sex hormones determined differences influence the health of an individual by influencing many physiological parameters. As the pulmonary functions are different between male and female and the susceptibility to different respiratory diseases varies between genders, this study has been designed to assess the relation between gender and the nasal mucociliary clearance, an inherent protective mechanism of the respiratory passages. Aim & objectives: To assess the relation between gender and nasal mucociliary clearance (NMC). Materials & methods: This cross sectional study was carried out on 60 randomly selected volunteers (30 male volunteers and 30 female volunteers) and NMC time was measured in them. The saccharin transit method was used to assess NMC. Saccharin transit time (STT) is the time taken by the participant to appreciate the taste of saccharin after placement of tablet of saccharin (1mm x 1mm) in the nostril. Results: The mean NMC in males was 7.71 2.35min and in the females was 7.65 2.22 min. There was no statistical significance as the p value is 0.9291. Conclusion: NMC time did not vary between male and female population. Therefore it could be inferred that gender has no apparent influence on nasal mucociliary clearance.

Orexin-1 receptor antagonist in central nucleus of the amygdala attenuates the acquisition of flavor-taste preference in rats

Previous studies demonstrated that the intracerebroventricular administration of SB-334867-A, a selective antagonist of orexin OX1R receptors, blocks the acquisition of saccharin-induced conditioned flavor preference (CFP) but not LiCl-induced taste aversion learning (TAL). Orexinergic fibers from the lateral hypothalamus end in the central nucleus of the amygdala (CeA), which expresses orexin OX1R receptors. Taste and sensory inputs also are present in CeA, which may contribute to the development of taste learning. This study analyzed the effect of two doses (1.5 and 6μg/0.5μl) of SB-334867-A administered into the CeA on flavor–taste preference induced by saccharin and on TAL induced by a single administration of LiCl (0.15M, 20ml/kg, i.p.). Outcomes indicate that inactivation of orexinergic receptors in the CeA attenuates flavor–taste preference in a two-bottle test (saccharin vs. water). Intra-amygdalar SB-334867-A does not affect gustatory processing or the preference for the sweet taste of saccharin given that SB-334867-A- and DMSO-treated groups (control animals) increased the intake of the saccharin-associated flavor across training acquisition sessions. Furthermore, SB-334867-A in the CeA does not block TAL acquisition ruling out the possibility that functional inactivation of OX1R receptors interferes with taste processing. Orexin receptors in the CeA appear to intervene in the association of a flavor with orosensory stimuli, e.g., a sweet and pleasant taste, but could be unnecessary when the association is established with visceral stimuli, e.g., lithium chloride. These data suggest that orexinergic projections to the CeA may contribute to the reinforcing signals facilitating the acquisition of taste learning and the change in hedonic evaluation of the taste, which would have important implications for the OX1R-targeted pharmacological treatment of eating disorders.

Mediation of the extinction process in behaviorally conditioned immunosuppression

To analyze neuro-immune-communication, our research group established a model of conditioned immunosuppression in rats which follows the principle of classical (Pavlovian) conditioning. We employed a conditioned taste aversion (CTA) paradigm where the novel taste saccharin (conditioned stimulus/CS) is paired with the immunosuppressive drug cyclosporine A (unconditioned stimulus/US). Upon re-exposure to the conditioned stimulus animals show a reduced CTA (saccharine intake), as well as a significant inhibition of T lymphocyte proliferation and IFN-γ and IL-2 in anti-CD3 stimulated splenic T cells. Repeated, unreinforced re-exposure to the CS leads to an extinction of the conditioned behavioral (CTA) and immune responses (cytokine inhibition, lymphocyte proliferation). In order to analyze the neurobiological mechanisms responsible for the extinction process we administered the protein synthesis inhibitor Anisomycin, or the beta-adrenergic receptor blocker Propranolol into the insular cortex during evocation, as the insular cortex is known to mediate the learned immune response during re-exposure of the CS. Our preliminary data show a prolonged extinction of the CTA reflected by a reduced CS intake after micro injection of protein synthesis inhibitor Anisomycin but not after administration of Propranolol into the insular cortex. Ongoing experiments will reveal whether the prolonged extinction on the behavioral level can also be detected in the conditioned immune response.

A drug-paired taste cue elicits withdrawal and predicts cocaine self-administration

Addiction is a chronic disease where periods of abstinence are riddled with instances of craving, withdrawal, and eventual relapse to escalated drug use. Cues previously associated with drug use can have a deleterious effect on this cycle by precipitating withdrawal symptoms. Here we focus specifically on the relationship between avoidance of a drug-paired taste cue and the ability of the drug-paired cue to elicit withdrawal and, ultimately, drug seeking and taking. We used a rat model of drug addiction and naloxone-induced loss of body weight to test whether a taste cue elicits withdrawal in anticipation of drug availability. Experiment 1 investigated the ability of a taste cue to elicit signs of withdrawal when it predicted experimenter-administered morphine (15mg/kg, i.p.). In Experiment 2, a saccharin taste cue was paired with the opportunity to actively self-administer cocaine (0.167mg/infusion, i.v.). The results show that presentation of a morphine- or cocaine-paired taste cue is sufficient to elicit naloxone-induced withdrawal symptoms, and greater withdrawal predicts greater cocaine self-administration in rats.

Glucocorticoids interact with the noradrenergic arousal system in the nucleus accumbens shell to enhance memory consolidation of both appetitive and aversive taste learning

It is well established that glucocorticoid hormones strengthen the consolidation of long-term memory of emotionally arousing experiences but have little effect on memory of low-arousing experiences. Although both positive and negative emotionally arousing events tend to be well remembered, studies investigating the neural mechanism underlying glucocorticoid-induced memory enhancement focused primarily on negatively motivated training experiences. In the present study we show an involvement of glucocorticoids within the nucleus accumbens (NAc) in enhancing memory consolidation of both an appetitive and aversive form of taste learning. The specific glucocorticoid receptor (GR) agonist RU 28362 (1 or 3ng) administered bilaterally into the NAc shell, but not core, of male Sprague–Dawley rats immediately after an appetitive saccharin drinking experience dose-dependently enhanced 24-h retention of the safe taste, resulting in a facilitated attenuation of neophobia. Similarly, GR agonist infusions given into the NAc shell immediately after pairing of the saccharin taste with a malaise-inducing agent enhanced memory of this negative experience, resulting in an intensified conditioned aversion. Importantly, a suppression of noradrenergic activity within the NAc shell with the β-adrenoceptor antagonist propranolol blocked the facilitating effect of a concurrently administered GR agonist on memory consolidation in both the appetitive and aversive learning task. Thus, these findings indicate that GR activation interacts with the noradrenergic arousal system within the NAc to enhance memory consolidation of emotionally arousing training experiences regardless of valence.

Lipopolysaccharide inhibits the simultaneous establishment of LiCl-induced anticipatory nausea and intravascularly conditioned taste avoidance in the rat

This study examined the effects of the bacterial endotoxin, lipopolysaccharide (LPS), on the establishment of anticipatory nausea and conditioned taste avoidance in a simultaneous conditioning paradigm using an intravascular/intraperitoneal saccharin taste. 83 naïve adult male Long-Evans rats were injected (intraperitoneal) with either 200μg/kg LPS or 0.9% saline (NaCl), 90min prior to ip treatment with either 64mg/kg LiCl, 64mg/kg LiCl+2.0% saccharin, 0.9% NaCl, or 0.9% NaCl+2.0% saccharin, and immediately placed into a distinctive context for 30min (repeated over 4 conditioning days, spaced 72h apart). 72h following the final conditioning day, each animal was re-exposed to the context on a drug-free test day where orofacial responding was recorded. The next day, animals received a 24h 2-bottle preference test with a choice between water and a palatable 0.2% saccharin solution. Results showed that LPS exposure, prior to LiCl or LiCl+Saccharin treatment, inhibited the establishment of anticipatory nausea, as evidenced by significantly lower conditioned gaping frequencies relative to animals pre-treated with NaCl followed by LiCl or LiCl+Saccharin. LPS pre-treatment also inhibited the formation of LiCl-induced taste avoidance, as evidence by significantly higher saccharin preferences in Group LPS–LiCl+Saccharin relative to Group NaCl–LiCl+Saccharin. The results of the current study provide additional evidence for the deleterious effects of LPS on learning and memory in aversive conditioning.

Taste neophobia and c-Fos expression in the rat brain

Taste neophobia refers to a reduction in consumption of a novel taste relative to when it is familiar. To gain more understanding of the neural basis of this phenomenon, the current study examined whether a novel taste (0.5% saccharin) supports a different pattern of c-Fos expression than the same taste when it is familiar. Results revealed that the taste ofthe novel saccharin solution evoked more Fos immunoreactivity than the familiar taste of saccharin in the basolateral region of the amygdala, central nucleus of the amygdala, gustatory portion of the thalamus, and the gustatory insular cortex. No such differential expressionwas found in the other examined areas, including the bed nucleus of stria terminalis,medial amygdala, and medial parabrachial nucleus. The present results are discussed with respect to a forebrain taste neophobia system.

Conditioned taste aversion from neostigmine or methyl-naloxonium in the nucleus accumbens

Taylor, K.M. Mark, G.P. Hoebel, B.G. Conditioned taste aversion from neostigmine or methyl-naloxonium in the nucleus accumbens Physiol Behav 00(00):000–000, 2011. An opioid antagonist injected in the nucleus accumbens of a morphine-dependent rat will lower extracellular dopamine and release acetylcholine (ACh), as also seen in opiate withdrawal. It was hypothesized that raising extracellular ACh experimentally would be aversive as reflected by the induction of a conditioned taste aversion. Rats were implanted with cannulas aimed above the nucleus accumbens (NAc) for injection of the opiate antagonist methyl-naloxonium in morphine-dependent animals or neostigmine to increase ACh in drug naïve animals. Experiment 1 in addicted rats showed that local morphine withdrawal by local injection of methyl-naloxonium paired with the taste of saccharin induces a conditioned taste aversion. Experiment 2 in non-addicted rats demonstrated the same learned aversion after local administration of the cholinergic agonist neostigmine in the NAc. These results suggest that ACh released in the NAc during opiate withdrawal contributes to the dysphoric, aversive state characteristic of withdrawal. This accumbens system is implicated in the mechanism for generating the memory of an aversive event that is expressed as learned taste aversion.

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.

The Conditioned Stimulus Elicits Taste Aversion but Not Sickness Behavior in Conditioned Mice

Objectives: This article extends previous reports on (i) elicitation of taste aversion after pairing a flavored beverage (saccharin solution) with a disease-provoking microbial product (lipopolysaccharide, LPS, or polyinosinic:polycytidylic acid, poly I:C); (ii) elicitation of sickness behavior (assessed as diminished ingestion of water and food) by the conditioned stimulus, and (iii) development of tolerance to those microbial products. Methods: Mice of the CD1 strain were conditioned by pairing ingestion of 0.15% saccharin solution with injection of LPS (100 µg/mouse) or poly I:C (6 mg/kg). A few days later, some mice were offered saccharin solution and were injected with saline, whereas other mice were offered saccharin solution and were injected with the microbial product. Results: Regardless of the nature of the unconditioned stimulus (LPS or poly I:C), (i) taste aversion to saccharin ensued, (ii) tolerance ensued to sickness elicitation by a second administration of the microbial component, and (iii) saccharin taste did not evoke sickness. Conclusions: Symptoms of infectious sickness in the absence of infection are hardly explained by exposure to the conditioned stimulus.