Fork this term
Forking concepts is the process of separating the senses, or variations, in the meaning of a term.
This process should be used sparingly, and the ability to fork a term is the sole provenance of the curator.
Asserted relationships to other concepts
| || |
are kinds of
|taste aversion|| |
is a kind of
| || |
are parts of
is a part of
is a kind of
is a part of
Tasks that are asserted to measure taste aversion
"Initial definition retrieved from http://en.wikipedia.org/wiki/Taste_aversion"
NPicchetti (about two years ago)
Definition contributed by BGregory about two years ago:occurs when the taste of a certain food is associated with symptoms caused by a toxic, spoiled, or poisonous substance; generally caused after ingestion of the food causes nausea, sickness, or vomiting. The ability to develop a taste aversion is considered an adaptive trait or survival mechanism that trains the body to avoid poisonous substances (e.g., poisonous berries) before they can cause harm.REVISION 2
Definition contributed by BGregory about three years ago:occurs when the taste of a certain food is associated with symptoms caused by a toxic, spoiled, or poisonous substance; generally caused after ingestion of the food causes nausea, sickness, or vomiting. The ability to develop a taste aversion is considered an adaptive trait or survival mechanism that trains the body to avoid poisonous substances (e.g., poisonous berries) before they can cause harm. (from Wikipedia)REVISION 1
Definition contributed by SAdministrator about four years ago:No definition submitted yetView Term Event Log
Term Event Log
2011-08-12 MChen: MChen updated the definition for taste aversion
2011-05-12 BGregory: BGregory updated the definition for taste aversion. [view the changes at http://cognitiveatlas.org/term/taste_aversion]
2011-05-11 NPicchetti: Added new topic to discussion
2010-05-06 BGregory: BGregory updated the definition for taste aversion. [view the changes at http://cognitiveatlas.org/term/taste_aversion]
Term BibliographyNo studies have been associated yet.
Nature.com Literature MatchesMatches have been found on Nature.com for taste aversion:
Nature Reviews Neuroscience (2004)
http://dx.doi.org/10.1038/nrn1344 [view abstract]
From an evolutionary point of view, one of the most important forms of memory is taste-recognition memory. When an animal eats, food-related cues are associated with the consequences of its ingestion. So, if a new taste is associated with malaise, animals will reject it on the next presentation, developing a long-lasting taste aversion. Conversely, when taste is not accompanied by digestive malaise, it becomes recognized as a safe signal, and the animal increases its consumption. In this review, the putative molecular signals and biochemical events that mediate the formation of safe and aversive taste-recognition memory traces are discussed.
Ilana Slouzkey, Kobi Rosenblum, Mouna Maroun
http://dx.doi.org/10.1038/npp.2013.20 [view abstract]
The conditioned taste aversion (CTA) paradigm, in which association between a novel taste and visceral malaise is formed, gives a unique experimental setting to examine the mechanisms underlying memory acquisition and extinction processes. AKT is a main kinase of the phosphoinositide 3-kinase cascade (PI3K) and has been implicated in long-term memory. We have recently reported that blockade of PI3K in the basolateral amygdala (BLA) before retrieval of fear memory was associated with long-term reduction in fear responses, suggesting a possible role of PI3K inhibition in fear erasure. In this study, we aimed to elucidate whether PI3K has a similar role in the insular cortex (IC), which has a crucial role in CTA acquisition, consolidation, maintenance, and extinction. To that end, we (1) monitored AKT phosphorylation in the IC following CTA acquisition and extinction and (2) inhibited PI3K by local microinjection of the PI3K inhibitor LY294002 at different stages of CTA acquisition and extinction. Our results show that while AKT phosphorylation is increased following CTA learning, it is decreased following CTA extinction. Inhibition of AKT phosphorylation in the IC before or after the first CTA retrieval test resulted in reduction in the aversion index. This reduction in aversion is due to the erasure of the original CTA trace memory, as re-application of the unconditioned stimulus (lithium chloride) did not induce the recovery of aversion in LY294002-treated animals. Our present data add new evidence to suggest that PI3K is engaged in consolidation of aversive memories, as its inhibition is associated with erasure of CTA memory.
Yuki Oka, Matthew Butnaru, Lars von Buchholtz, Nicholas J. P. Ryba, Charles S. Zuker
http://dx.doi.org/10.1038/nature11905 [view abstract]
In the tongue, distinct classes of taste receptor cells detect the five basic tastes; sweet, sour, bitter, sodium salt and umami. Among these qualities, bitter and sour stimuli are innately aversive, whereas sweet and umami are appetitive and generally attractive to animals. By contrast, salty taste is unique in that increasing salt concentration fundamentally transforms an innately appetitive stimulus into a powerfully aversive one. This appetitive–aversive balance helps to maintain appropriate salt consumption, and represents an important part of fluid and electrolyte homeostasis. We have shown previously that the appetitive responses to NaCl are mediated by taste receptor cells expressing the epithelial sodium channel, ENaC, but the cellular substrate for salt aversion was unknown. Here we examine the cellular and molecular basis for the rejection of high concentrations of salts. We show that high salt recruits the two primary aversive taste pathways by activating the sour- and bitter-taste-sensing cells. We also demonstrate that genetic silencing of these pathways abolishes behavioural aversion to concentrated salt, without impairing salt attraction. Notably, mice devoid of salt-aversion pathways show unimpeded, continuous attraction even to very high concentrations of NaCl. We propose that the ‘co-opting’ of sour and bitter neural pathways evolved as a means to ensure that high levels of salt reliably trigger robust behavioural rejection, thus preventing its potentially detrimental effects on health.
Yali V Zhang, Rakesh P Raghuwanshi, Wei L Shen, Craig Montell
Nature Neuroscience (2013)
http://dx.doi.org/10.1038/nn.3513 [view abstract]
Animals tend to reject bitter foods. However, long-term exposure to some unpalatable tastants increases acceptance of these foods. Here we show that dietary exposure to an unappealing but safe additive, camphor, caused the fruit fly Drosophila melanogaster to decrease camphor rejection. The transient receptor potential-like (TRPL) cation channel was a direct target for camphor in gustatory receptor neurons, and long-term feeding on a camphor diet led to reversible downregulation of TRPL protein concentrations. The turnover of TRPL was controlled by an E3 ubiquitin ligase, Ube3a. The decline in TRPL levels and increased acceptance of camphor reversed after returning the flies to a camphor-free diet long term. We propose that dynamic regulation of taste receptors by ubiquitin-mediated protein degradation comprises an important molecular mechanism that allows an animal to alter its taste behavior in response to a changing food environment.
Sandhya Charlu, Zev Wisotsky, Adriana Medina, Anupama Dahanukar
Nature Communications (2013)
http://dx.doi.org/10.1038/ncomms3042 [view abstract]
Drosophila melanogaster can taste various compounds and separate them into few basic categories such as sweet, bitter and salt taste. Here we investigate mechanisms underlying acid detection in Drosophila and report that the fly displays strong taste aversion to common carboxylic acids. We find that acid tastants act by the activation of a subset of bitter neurons and inhibition of sweet neurons. Bitter neurons begin to respond at pH 5 and show an increase in spike frequency as the extracellular pH drops, which does not rely on previously identified chemoreceptors. Notably, sweet neuron activity depends on the balance of sugar and acid tastant concentrations. This is independent of bitter neuron firing, and allows the fly to avoid acid-laced food sources even in the absence of functional bitter neurons. The two mechanisms may allow the fly to better evaluate the risk of ingesting acidic foods and modulate its feeding decisions accordingly.
H E Wilson-Pérez, A P Chambers, D A Sandoval, M A Stefater, S C Woods, S C Benoit, R J Seeley
International Journal of Obesity (2012)
http://dx.doi.org/10.1038/ijo.2012.18 [view abstract]
Diets high in fat are implicated in the development and maintenance of obesity, and obese individuals display greater preferences for high-fat foods than do their lean counterparts. Weight-reduction bariatric surgery is associated with changes in food choice. In particular, after Roux-en-Y gastric bypass (RYGB), humans and rodents select or prefer foods that are lower in fat content. We asked whether a bariatric surgical procedure limited to the stomach, vertical sleeve gastrectomy (VSG), causes a similar reduction of fat intake/preference. Rats received VSG or Sham surgery or remained surgically naïve, and were assessed for food preference using three diet-choice paradigms. Using progressive-ratio (PR) and conditioned taste aversion paradigms, we further asked whether surgically induced changes in food choice are secondary to changes in the reward value of food and/or to the formation of a food aversion. Finally, food choice was compared between VSG- and RYGB-operated rats. VSG rats decreased their intake of dietary fat, and shifted their preference toward lower caloric-density foods. This change in food choice was not associated with changes in motivated responding on a PR schedule for either a fat or a carbohydrate food reinforcer. When VSG and RYGB were compared directly, both procedures caused comparable changes in food choice. The conditioned taste aversion paradigm revealed that VSG rats form an aversion to an intra-gastric oil administration whereas RYGB rats do not. VSG and RYGB, two anatomically distinct bariatric procedures, produce similar changes in food choice.
Diets high in fat are implicated in the development and maintenance of obesity, and obese individuals display greater preferences for high-fat foods than do their lean counterparts. Weight-reduction bariatric surgery is associated with changes in food choice. In particular, after Roux-en-Y gastric bypass (RYGB), humans and rodents select or prefer foods that are lower in fat content. We asked whether a bariatric surgical procedure limited to the stomach, vertical sleeve gastrectomy (VSG), causes a similar reduction of fat intake/preference.RESEARCH DESIGN AND METHODS:
Rats received VSG or Sham surgery or remained surgically naïve, and were assessed for food preference using three diet-choice paradigms. Using progressive-ratio (PR) and conditioned taste aversion paradigms, we further asked whether surgically induced changes in food choice are secondary to changes in the reward value of food and/or to the formation of a food aversion. Finally, food choice was compared between VSG- and RYGB-operated rats.RESULTS:
VSG rats decreased their intake of dietary fat, and shifted their preference toward lower caloric-density foods. This change in food choice was not associated with changes in motivated responding on a PR schedule for either a fat or a carbohydrate food reinforcer. When VSG and RYGB were compared directly, both procedures caused comparable changes in food choice. The conditioned taste aversion paradigm revealed that VSG rats form an aversion to an intra-gastric oil administration whereas RYGB rats do not.CONCLUSIONS:
VSG and RYGB, two anatomically distinct bariatric procedures, produce similar changes in food choice.
International Journal of Obesity (2004)
http://dx.doi.org/10.1038/sj.ijo.0802532 [view abstract]
The role of parental behaviour in the development of food preferences is considered. Food preferences develop from genetically determined predispositions to like sweet and salty flavours and to dislike bitter and sour tastes. Particularly towards the second year of life, there is a tendency to avoid novel foods (neophobia). Food aversions can be learnt in one trial if consumption is followed by discomfort. There is a predisposition to learn to like foods with high-energy density. However, from birth genetic predispositions are modified by experience and in this context during the early years parents play a particularly important role. Parental style is a critical factor in the development of food preferences. Children are more likely to eat in emotionally positive atmospheres. Siblings, peers and parents can act as role models to encourage the tasting of novel foods. Repeated exposure to initially disliked foods can breakdown resistance. The offering of low-energy-dense foods allows the child to balance energy intake. Restricting access to particular foods increases rather than decreases preference. Forcing a child to eat a food will decrease the liking for that food. Traditionally, educational strategies have typically involved attempts to impart basic nutritional information. Given the limited ability of information to induce changes in behaviour, an alternative strategy would be to teach parents about child development in the hope that an understanding of the characteristic innate tendencies and developmental stages can be used to teach healthy food preferences.
Urs Meyer, De Li Tilly Chang, Joram Feldon, Benjamin K Yee
http://dx.doi.org/10.1038/sj.npp.1300522 [view abstract]
In classical conditioning, pre-exposures to either the to-be-conditioned stimulus (CS) or unconditioned stimulus (US) can retard subsequent conditioning between the CS and US. The present experiment evaluated the expression of these two pre-exposure effects in mice of the C57BL6/J strain, one of the most common background strains for genetically altered mice. We tested whether their expression would be disrupted by amphetamine treatment (2.5 mg/kg, i.p.) in a conditioned taste aversion paradigm with sucrose as the CS and lithium chloride-induced gastric malaise as the US. We found that one pre-exposure (PE) to either the CS or the US reduced aversion to sucrose solution in the controls following conditioning, but no such tendency was evident in the amphetamine-treated mice. The present study represents the first report of amphetamine-induced disruption of the CS-PE effect (ie latent inhibition) in mice, and the first attempt to compare it directly with the US-PE effect in any species. It extended previous reports in rats and humans, suggesting that the sensitivity of latent inhibition to amphetamine is largely comparable across species, thereby lending credence to the use of the latent inhibition effect as a behavioral assay for psychotic-like phenotype in transgenic mice. The parallel observation in the US-PE effect further indicates that its expression, at least in the present conditioned taste aversion paradigm, may also be under similar influence of the dopaminergic system.
http://dx.doi.org/10.1038/sj.npp.1301050 [view abstract]
The ability to extinguish aversive memories is of significant clinical interest. The amygdala plays an important role in emotional conditioning and its experimental extinction. It has been suggested that γ-aminobutyric acid (GABA) agonists retard extinction and that consolidation of extinction involves N-methyl-D-aspartate receptor (NMDAR)-mediated plasticity. The aim was to further explore the interaction between GABA and NMDA in the amygdala in consolidation of experimental extinction in the rat. To that end conditioned taste aversion (CTA) was used. In CTA, the amygdala has been reported to subserve both acquisition and extinction. The GABAA receptor agonist, muscimol, administered into the amygdala immediately after the first extinction session, caused lasting disruption of extinction of CTA for at least 2 weeks. However, the administration of GABAA receptor antagonists had no effect on extinction kinetics. Microinfusing the partial NMDA agonist D-cycloserine together with or after muscimol infusion reversed the blocking effects of muscimol. These findings could bear relevance to the potential involvement of extinction abnormalities in behavioral disorders, and their amelioration.
David V. Smith, Robert F. Margolskee
Scientific American (2001)
http://dx.doi.org/10.1038/scientificamerican0301-32 [view abstract]
How do cells on the tongue register the sensations of sweet, salty, sour and bitter? Scientists are finding out—and discovering how the brain interprets these signals as various tastes
Taban Seif, Shao-Ju Chang, Jeffrey A Simms, Stuart L Gibb, Jahan Dadgar, Billy T Chen, Brandon K Harvey, Dorit Ron, Robert O Messing, Antonello Bonci, F Woodward Hopf
Nature Neuroscience (2013)
http://dx.doi.org/10.1038/nn.3445 [view abstract]
Compulsive drinking despite serious adverse medical, social and economic consequences is a characteristic of alcohol use disorders in humans. Although frontal cortical areas have been implicated in alcohol use disorders, little is known about the molecular mechanisms and pathways that sustain aversion-resistant intake. Here, we show that nucleus accumbens core (NAcore) NMDA-type glutamate receptors and medial prefrontal (mPFC) and insula glutamatergic inputs to the NAcore are necessary for aversion-resistant alcohol consumption in rats. Aversion-resistant intake was associated with a new type of NMDA receptor adaptation, in which hyperpolarization-active NMDA receptors were present at mPFC and insula but not amygdalar inputs in the NAcore. Accordingly, inhibition of Grin2c NMDA receptor subunits in the NAcore reduced aversion-resistant alcohol intake. None of these manipulations altered intake when alcohol was not paired with an aversive consequence. Our results identify a mechanism by which hyperpolarization-active NMDA receptors under mPFC- and insula-to-NAcore inputs sustain aversion-resistant alcohol intake.
Ken L. Mueller, Mark A. Hoon, Isolde Erlenbach, Jayaram Chandrashekar, Charles S. Zuker, Nicholas J. P. Ryba
http://dx.doi.org/10.1038/nature03352 [view abstract]
The sense of taste provides animals with valuable information about the nature and quality of food. Bitter taste detection functions as an important sensory input to warn against the ingestion of toxic and noxious substances. T2Rs are a family of approximately 30 highly divergent G-protein-coupled receptors (GPCRs) that are selectively expressed in the tongue and palate epithelium and are implicated in bitter taste sensing. Here we demonstrate, using a combination of genetic, behavioural and physiological studies, that T2R receptors are necessary and sufficient for the detection and perception of bitter compounds, and show that differences in T2Rs between species (human and mouse) can determine the selectivity of bitter taste responses. In addition, we show that mice engineered to express a bitter taste receptor in ‘sweet cells’ become strongly attracted to its cognate bitter tastants, whereas expression of the same receptor (or even a novel GPCR) in T2R-expressing cells resulted in mice that are averse to the respective compounds. Together these results illustrate the fundamental principle of bitter taste coding at the periphery: dedicated cells act as broadly tuned bitter sensors that are wired to mediate behavioural aversion.
Sidney A. Simon, Ivan E. de Araujo, Ranier Gutierrez, Miguel A. L. Nicolelis
Nature Reviews Neuroscience (2006)
http://dx.doi.org/10.1038/nrn2006 [view abstract]
Whenever food is placed in the mouth, taste receptors are stimulated. Simultaneously, different types of sensory fibre that monitor several food attributes such as texture, temperature and odour are activated. Here, we evaluate taste and oral somatosensory peripheral transduction mechanisms as well as the multi-sensory integrative functions of the central pathways that support the complex sensations that we usually associate with gustation. On the basis of recent experimental data, we argue that these brain circuits make use of distributed ensemble codes that represent the sensory and post-ingestive properties of tastants.
Jayaram Chandrashekar, Christina Kuhn, Yuki Oka, David A. Yarmolinsky, Edith Hummler, Nicholas J. P. Ryba, Charles S. Zuker
http://dx.doi.org/10.1038/nature08783 [view abstract]
Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion. Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, whereas the aversive one functions as a non-selective detector for a wide range of salts. Because amiloride is a potent inhibitor of the epithelial sodium channel (ENaC), ENaC has been proposed to function as a component of the salt-taste-receptor system. Previously, we showed that four of the five basic taste qualities—sweet, sour, bitter and umami—are mediated by separate taste-receptor cells (TRCs) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses. Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC, and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaCα in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses. Together, these studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.
Jayaram Chandrashekar, Mark A. Hoon, Nicholas J. P. Ryba, Charles S. Zuker
http://dx.doi.org/10.1038/nature05401 [view abstract]
The emerging picture of taste coding at the periphery is one of elegant simplicity. Contrary to what was generally believed, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes: sweet, sour, bitter, salty and umami. Importantly, receptor cells for each taste quality function as dedicated sensors wired to elicit stereotypic responses.
Luis Ruiz-Avila, Susan K. McLaughlin, David Wildman, Peter J. McKinnon, Alain Robichon, Nancy Spickofsky, Robert F. Margolskee
http://dx.doi.org/10.1038/376080a0 [view abstract]
Using the polymerase chain reaction (PCR), we isolated clones for the a-subunits of rod and cone transducin from a taste cell complementary DNA library. The entire coding sequence of rat rod transducin (at.
J. GIBBS, G. P. SMITH
http://dx.doi.org/10.1038/266196b0 [view abstract]
GIBBS and SMITH reply-The production of a conditioned taste aversion, using a single dose of the synthetic octapeptide of CCK as the unconditioned stimulus, is not a critical test of the hypothesis that CCK mediates all or part of the satiety effect of food in the intestine. One indirect test of the hypothesis using the taste aversion paradigm would be the comparison of dose-response curves for both satiety and taste aversion.
R. FISCHER, F. GRIFFIN, S. ENGLAND, S. M. GARN
http://dx.doi.org/10.1038/1911328a0 [view abstract]
In the present work, forty-eight subjects checked food dislikes and aversions on an alphabetical listing of 118 foods previously tested on a college-age Ohio population3. Excluding foods unfamiliar or never sampled by each subject, the percentage of familiar foods disliked was used as the individual score.
C C Boer, M E P Correa, E C M Miranda, C A de Souza
Bone Marrow Transplantation (2009)
http://dx.doi.org/10.1038/bmt.2009.237 [view abstract]
The aim of this study was to evaluate taste perception, salivary flow rate and oral pathologies in three different groups of patients undergoing hematopoietic SCT (HSCT) classified according to time post transplant. Group I (n=20) up to 150 days after HSCT, group II (n=20) between 151 and 1095 days and group III (n=21) more than 1095 days. Taste acuity was measured by four basic tastes of four solutions, in three concentrations (M): NaCl, sucrose, citric acid and caffeine. Patients classified flavors as sweet, sour, salty, bitter and without flavor. The intensity was considered high, medium and low. Unstimulated saliva was collected and salivary flow rates (ml/min) were determined. Of 61 patients, 31 had chronic GVHD. For the sweet solution, the high and low concentrations represented a challenge for those patients. No patients were sensitive to the low concentration of caffeine solution (P=0.05). Saliva flow rate was diminished in 10 of 61 (16%) patients and hyposalivation was more intense in groups II/III (P=0.007). There was no correlation between taste dysfunction and oral chronic GVHD. The results indicated taste alterations only for the sweet and salty tastes even in patients up to 3 years after HSCT and may not correlate with oral chronic GVHD and with hyposalivation.
J. A. Deutsch
http://dx.doi.org/10.1038/285592a0 [view abstract]
IT has recently been claimed by Gibbs et al.1 that bombesin (BBS), like cholecystokinin (CCK), produces satiety in rats. However, their report ignores crucial evidence and lacks critical controls.
I E de Araujo, S A Simon
International Journal of Obesity (2009)
http://dx.doi.org/10.1038/ijo.2009.70 [view abstract]
The central gustatory pathways are part of the brain circuits upon which rest the decision to ingest or reject a food. The quality of food stimuli, however, relies not only on their taste but also on properties such as odor, texture and temperature. We will review anatomical and functional evidence showing that the central gustatory system, in particular its cortical aspect, functions as an integrative circuit in which taste-responsive neurons also show sensitivity to somatosensory and olfactory stimulation. In addition, gustatory pathways are modulated by the internal state of the body, with neuronal responses to tastes changing according to variations in physiological parameters such as gastrointestinal hormones or blood glucose levels. Therefore, rather than working as the receptive field of peripheral taste receptor cells, the central gustatory pathways seem to operate as a multisensory system dedicated to evaluating the biological significance of intra-oral stimuli.
Alina Elkobi, Ingrid Ehrlich, Katya Belelovsky, Liza Barki-Harrington, Kobi Rosenblum
Nature Neuroscience (2008)
http://dx.doi.org/10.1038/nn.2190 [view abstract]
The processes underlying long-term memory formation in the neocortex are poorly understood. Using taste learning, we found learning-related induction of PSD-95 in the gustatory cortex, which was temporally restricted, coupled to the learning of a novel, but not familiar, taste and controlled by ERK. Using temporally and spatially restricted RNA interference knockdown of PSD-95 in vivo, we found that PSD-95 induction is necessary for learning novel tastes, but not for the recollection of familiar ones.
http://dx.doi.org/10.1038/35093032 [view abstract]
Taste is the sensory system devoted primarily to a quality check of food to be ingested. Although aided by smell and visual inspection, the final recognition and selection relies on chemoreceptive events in the mouth. Emotional states of acute pleasure or displeasure guide the selection and contribute much to our quality of life. Membrane proteins that serve as receptors for the transduction of taste have for a long time remained elusive. But screening the mass of genome sequence data that have recently become available has provided a new means to identify key receptors for bitter and sweet taste. Molecular biology has also identified receptors for salty, sour and umami taste.
Nirupa Chaudhari, Ana Marie Landin, Stephen D. Roper
Nature Neuroscience (2000)
http://dx.doi.org/10.1038/72053 [view abstract]
Sensory transduction for many taste stimuli such as sugars, some bitter compounds and amino acids is thought to be mediated via G protein-coupled receptors (GPCRs), although no such receptors that respond to taste stimuli are yet identified. Monosodium L-glutamate (l-MSG), a natural component of many foods, is an important gustatory stimulus believed to signal dietary protein. We describe a GPCR cloned from rat taste buds and functionally expressed in CHO cells. The receptor couples negatively to a cAMP cascade and shows an unusual concentration–response relationship. The similarity of its properties to MSG taste suggests that this receptor is a taste receptor for glutamate.
Jack B Nitschke, Gregory E Dixon, Issidoros Sarinopoulos, Sarah J Short, Jonathan D Cohen, Edward E Smith, Stephen M Kosslyn, Robert M Rose, Richard J Davidson
Nature Neuroscience (2006)
http://dx.doi.org/10.1038/nn1645 [view abstract]
The primary taste cortex consists of the insula and operculum. Previous work has indicated that neurons in the primary taste cortex respond solely to sensory input from taste receptors and lingual somatosensory receptors. Using functional magnetic resonance imaging, we show here that expectancy modulates these neural responses in humans. When subjects were led to believe that a highly aversive bitter taste would be less distasteful than it actually was, they reported it to be less aversive than when they had accurate information about the taste and, moreover, the primary taste cortex was less strongly activated. In addition, the activation of the right insula and operculum tracked online ratings of the aversiveness for each taste. Such expectancy-driven modulation of primary sensory cortex may affect perceptions of external events.
J. GIBBS, G. P. SMITH
http://dx.doi.org/10.1038/285592b0 [view abstract]
GIBBS AND SMITH REPLY-We did not use a conditioned taste aversion paradigm in our study of the effect of bombesin (BBS) on feeding1 because this paradigm can no longer be considered a critical test of the presence or absence of malaise2. As a variety of agents (including isotonic saline and chlorpromazine, a drug with anti-nausea action) which serve as effective unconditioned stimuli for the formation of conditioned taste aversions3,4 do not produce sickness, the conditioned taste aversion test cannot be used as evidence of sickness.
Yaihara Fortis-Santiago, Benjamin A Rodwin, Selin Neseliler, Caitlin E Piette, Donald B Katz
Nature Neuroscience (2009)
http://dx.doi.org/10.1038/nn.2463 [view abstract]
As anyone who has suffered through a head cold knows, food eaten when the olfactory system is impaired tastes 'wrong', an experience that leads many to conclude that taste stimuli are processed normally only when the olfactory system is unimpaired. Evidence that the taste system influences olfactory perception, however, has been vanishingly rare. We found just such an influence; if taste cortex was inactivated when an odor was first presented, later presentations were properly appreciated only if taste cortex was again inactivated.
Bijal P. Trivedi
http://dx.doi.org/10.1038/ontol464S7a [view abstract]
Research into human taste receptors extends beyond the tongue to some unexpected places.
Luis Stinus, Martine Cador, Eric P Zorrilla, George F Koob
http://dx.doi.org/10.1038/sj.npp.1300487 [view abstract]
Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague–Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 μg/kg, s.c.) to one arm of a three-chambered place conditioning apparatus. Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal. A corticotropin-releasing factor-1 (CRF1) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF1 antagonists can block the aversive stimulus effects of opiate withdrawal and may be potential therapeutic targets for opiate dependence.
GEORGE WOLF, GEORGE H. LAWRENCE
http://dx.doi.org/10.1038/2001025a0 [view abstract]
Hoshishima et al3 have recently examined this phenomenon in mice presented with various taste substances. These workers report no saline preference and report unusually high discrimination (aversion) thresholds for all strains used.
L. MUMFORD, A. R. TEIXEIRA, R. KUMAR
http://dx.doi.org/10.1038/272167a0 [view abstract]
Sixty male hooded rats aged about 60 d were given solutions of morphine to drink instead of tapwater for 52 d, and from then on their access to fluids was restricted to 2 h each day, between HOOh and 1300h. After 14 d of restricted access to only morphine solutions, the rats were given 12 choice tests between morphine solutions and water, alternating with 12 d when morphine solutions alone were provided.
O Della-Zuana, L Revereault, A Beck-Sickinger, A Monge, D-H Caignard, J-L Fauchère, J-M Henlin, V Audinot, J A Boutin, S Chamorro, M Félétou, N Levens
International Journal of Obesity (2004)
http://dx.doi.org/10.1038/sj.ijo.0802435 [view abstract]
AIM: These studies were performed to test the hypothesis that endogenous neuropeptide Y (NPY) acting on the NPY Y5 receptor subtype contributes to the control of food intake. The hypothesis was tested using S 25585—a newly synthesized NPY Y5 receptor antagonist.
METHODS AND RESULTS: S 25585 was shown to be a high-affinity antagonist of the NPY Y5 receptor subtype (IC50 5 nM) with no significant affinity toward other NPY receptor subtypes and over 40 other receptors, channels or uptake systems. S 25585 (7.5 mg/kg, i.p.) did not induce a conditioned taste aversion, significantly alter need-induced sodium appetite or induce pica, suggesting that at this dose the compound did not induce illness or malaise. In satiated rats, S 25585 (5.0 and 7.5 mg/kg, i.p.) significantly decreased the overfeeding induced by i.c.v. injection of NPY (1 μg) and the highly selective NPY Y5 receptor agonist [hPP1−17, Ala31, Aib32]NPY (0.7 μg). In rats fasted for 4 h immediately before the dark phase, analysis of the microstructure of feeding behavior revealed that S 25585 significantly increased latency to eat and significantly decreased the duration and size of the meals without altering the meal number or eating rate. Analysis of the behavioral satiety sequence at this time revealed that the animals passed through the normal pattern of feeding, grooming and resting. Although S 25585 appeared to be influencing a physiological system controlling appetite, this does not involve the NPY Y5 receptor since the antagonist also markedly reduced food intake in the NPY Y5 knockout mouse.
CONCLUSIONS: The results presented do not support a role for the NPY Y5 receptor in the control of food intake. The results further illustrate that it is imperative that the activity of any new NPY Y5 antagonist be assessed in the NPY Y5 knockout mouse before assuming that its effect on food intake is due to blockade of this receptor.
G. van Dijk, T. E. Thiele, R. J. Seeley, S. C. Woods, I. L. Bernstein
http://dx.doi.org/10.1038/385214a0 [view abstract]
On the basis of their observation that intracerebroventricular administration of glucagon-like peptide-1 (residues 7-36) amide (GLP-1) reduced food intake in rats, Turton et aV suggest that GLP-1 is a physiological mediator of satiety. Using c-Fos immunohistochemistry as a marker of neuronal activity, they reported that GLP-1 induces c-Fos expression "exclusively" in the paraventricular hypothalamus and central amygdala, regions of the brain important in the regulation of feeding.
Nora V Bergasa
American Journal of Gastroenterology (1998)
http://dx.doi.org/10.1111/j.1572-0241.1998.00396.x [view abstract]
Patients with liver disease experience alterations in the sense of taste. There is increasing evidence to suggest that some of the symptoms associated with liver disease (e.g., pruritus) are mediated in the brain. A hypothesis for a brain-mediated mechanism underlying taste alterations in hepatic disorders is presented in this paper.
Antoine Bechara, Derek van der Kooy
http://dx.doi.org/10.1038/314533a0 [view abstract]
The microinjection of morphine directly into certain specific brain sites can produce positive reinforcing effects similar to those seen after systemically administered drug1. The central dose required to produce these effects is lower than that needed to produce similar effects after systemic administration, suggesting that the primary population of receptors mediating the positive reinforcing effects is localized in the brain6.
B A Gosnell, A S Levine
International Journal of Obesity (2009)
http://dx.doi.org/10.1038/ijo.2009.73 [view abstract]
Humans eat for many reasons, including the rewarding qualities of foods. A host of neurotransmitters have been shown to influence eating behavior and some of these appear to be involved in reward-induced eating. Endogenous opioid peptides and their receptors were first reported more than 30 years ago, and studies suggesting a role of opioids in the regulation of food intake date back nearly as far. Opioid agonists and antagonists have corresponding stimulatory and inhibitory effects on feeding. In addition to studies aimed at identifying the relevant receptor subtypes and sites of action within the brain, there has been a continuing interest in the role of opioids on diet/taste preferences, food reward, and the overlap of food reward with others types of reward. Data exist that suggest a role for opioids in the control of appetite for specific macronutrients, but there is also evidence for their role in the stimulation of intake based on already-existing diet or taste preferences and in controlling intake motivated by hedonics rather than by energy needs. Finally, various types of studies indicate an overlap between mechanisms mediating drug reward and palatable food reward. Preference or consumption of sweet substances often parallels the self-administration of several drugs of abuse, and under certain conditions, the termination of intermittent access to sweet substances produces symptoms that resemble those observed during opiate withdrawal. The overconsumption of readily available and highly palatable foods likely contributes to the growing rates of obesity worldwide. An understanding of the role of opioids in mediating food reward and promoting the overconsumption of palatable foods may provide insights into new approaches for preventing obesity.
Angela Wagner, Howard Aizenstein, Laura Mazurkewicz, Julie Fudge, Guido K Frank, Karen Putnam, Ursula F Bailer, Lorie Fischer, Walter H Kaye
http://dx.doi.org/10.1038/sj.npp.1301443 [view abstract]
Anorexia nervosa (AN) is an illness characterized by aversion to ingestion of normally palatable foods. We examined whether there is a primary disturbance of taste processing and experience of pleasure using a sucrose/water task in conjunction with functional magnetic resonance imaging (fMRI). To avoid confounding effects of illness, 16 women recovered from restricting-type AN were compared to 16 control women (CW). We used a region of interest-based fMRI approach to test the idea that individuals with AN have differential neural activation in primary and secondary taste cortical regions after sucrose and water administration. Compared to CW, individuals recovered from AN showed a significantly lower neural activation of the insula, including the primary cortical taste region, and ventral and dorsal striatum to both sucrose and water. In addition, insular neural activity correlated with pleasantness ratings for sucrose in CW, but not in AN subjects. Altered taste processing may occur in AN, based on differences in activity in insular–striatal circuits. These data provide the first evidence that individuals with AN process taste stimuli differently than controls, based on differences in neural activation patterns.
JA Levine, PW Emery
British Journal of Cancer (1987)
http://dx.doi.org/10.1038/bjc.1987.157 [view abstract]
The results of 24 h food preference tests have suggested that learned food aversions may be involved in the development of anorexia in tumour bearing rats and in patients with cancer. We have performed similar tests over longer periods, up to 10 days, in male rats implanted with Leydig cell tumours, using semisynthetic diets containing differing proportions of fat, protein and carbohydrate. Tumour growth caused anorexia (16-30% decrease in food intake) and cachexia (78% decrease in body fat and 18% decrease in body protein, but 16% increase in body water). Both tumour bearing and control rats preferred a high carbohydrate diet to a high fat diet regardless of their previous diet: tumour bearing rats showed no evidence of a learned food aversion in these experiments. Tumour bearing rats did show an initial preference for a novel high protein diet when this was offered as an alternative to the normal protein diet they had previously been consuming, but this apparent learned food aversion disappeared on the second day of the test and was in fact reversed on all the subsequent days of the test. However, tumour bearing rats did show a sustained preference for a novel low protein diet when this was offered as an alternative to the normal protein diet they had previously been consuming. These results suggest that anorexia in the tumour bearing rats was not caused by a learned food aversion. However the results do indicate that the tumour bearing rats may have developed a specific aversion to protein in the diet. Leydig cell tumours are known to secrete large amounts of oestradiol. However injections of oestradiol in normal male rats caused an increase in body fat content and had no effect on the rats' preference for dietary protein. Clearly hypersecretion of oestradiol was not responsible for the loss of body fat, the fluid retention and the aversion to dietary protein which characterised the tumour bearing rats. The mechanisms by which tumour growth causes anorexia and cachexia in these rats remains obscure.
Segev Barak, Feng Liu, Sami Ben Hamida, Quinn V Yowell, Jeremie Neasta, Viktor Kharazia, Patricia H Janak, Dorit Ron
Nature Neuroscience (2013)
http://dx.doi.org/10.1038/nn.3439 [view abstract]
Relapse to alcohol abuse is an important clinical issue that is frequently caused by cue-induced drug craving. Therefore, disruption of the memory for the cue-alcohol association is expected to prevent relapse. It is increasingly accepted that memories become labile and erasable soon after their reactivation through retrieval during a memory reconsolidation process that depends on protein synthesis. Here we show that reconsolidation of alcohol-related memories triggered by the sensory properties of alcohol itself (odor and taste) activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions in rats, resulting in increased levels of several synaptic proteins. Furthermore, systemic or central amygdalar inhibition of mTORC1 during reconsolidation disrupts alcohol-associated memories, leading to a long-lasting suppression of relapse. Our findings provide evidence that the mTORC1 pathway and its downstream substrates are crucial in alcohol-related memory reconsolidation and highlight this pathway as a therapeutic target to prevent relapse.
http://dx.doi.org/10.1038/468S18a [view abstract]
Certain things taste differently to different people. Why is this, and does this affect our choice of food?
Stéphanie Caillé, Luis Stinus, Emilio F Espejo, Philippe De Deurwaerdère, Umberto Spampinato, George F Koob
http://dx.doi.org/10.1038/sj.npp.1300033 [view abstract]
Previous pharmacological studies have implicated serotonergic brain systems in opiate-withdrawal-precipitated conditioned place aversion. To assess this hypothesis, we tested the effects of either (i) a near-total 5,7-dihydroxytryptamine-induced lesion (90% depletion) or (ii) an acute serotonin (5-HT) inhibition induced by the specific stimulation of 5-HT1A autoreceptors (8-OHDPAT 5–100 μg/kg), on naloxone-induced conditioned place aversion in morphine-dependent rats. Morphine dependence was induced by the implantation of morphine slow-release pellets. The protective properties of clonidine (an alpha-2 adrenergic agonist classically given for opiate detoxification) were also tested after inhibition of 5-HT transmission. Serotonergic lesions in morphine-dependent rats failed to alter naloxone-induced conditioned place aversion but increased the sensitivity to the protective effects of clonidine. Acute neuropharmacological blockade of serotonin transmission also potentiated the clonidine effects on naloxone-induced conditioned place aversion. When combined with the 5-HT1A agonist 8-OHDPAT, clonidine was also found to be more potent. Further understanding of this serotonin/noradrenaline interaction might help devise new therapeutic treatments for the acute opiate withdrawal syndrome.
Mads Tang-Christensen, Philip Just Larsen, Jesper Thulesen, John Rømer, Niels Vrang
Nature Medicine (2000)
http://dx.doi.org/10.1038/77535 [view abstract]
The dorsomedial hypothalamic nucleus harbors leptin sensitive neurons and is intrinsically connected to hypothalamic nuclei involved in feeding behavior. However, it also receives ascending input from the visceroceptive neurons of the brainstem. We have identified a unique glucagon-like-peptide-2 containing neuronal pathway connecting the nucleus of the solitary tract with the dorsomedial hypothalamic nucleus. A glucagon-like-peptide-2 fiber plexus targets neurons expressing its receptor within the dorsomedial hypothalamic nucleus. Pharmacological and behavioral studies confirmed that glucagon-like-peptide-2 signaling is a specific transmitter inhibiting rodent feeding behavior and with potential long-term effects on body weight homeostasis. The glucagon-like-peptide-1 receptor antagonist, Exendin (9–39) is also a functional antagonist of centrally applied glucagon-like-peptide-2.
Nature Reviews Neuroscience (2007)
http://dx.doi.org/10.1038/nrn2240 [view abstract]
The neocortex is presumed to be the ultimate repository of many types of long-term memory, but little is known about the mechanisms that underlie memory preservation. Dudai and colleagues have now demonstrated that inhibiting the enzyme protein kinase Mζ (PKMζ) , which was previously shown to be crucial for maintaining hippocampal long-term potentiation (LTP) and spatial memory, rapidly and perhaps permanently erases a long-term memory in the rat neocortex.
Nature Reviews Neuroscience (2003)
http://dx.doi.org/10.1038/nrn1240 [view abstract]
Reconsolidation — the idea that a memory, once retrieved, returns to a labile state that is susceptible to interference and must be reconsolidated into long-term storage — is controversial and surrounded by apparently conflicting data. New results from Eisenberg et al . might help to reconcile some of these findings.
Ralph Adolphs, Daniel Tranel, Michael Koenigs, Antonio R Damasio
Nature Neuroscience (2005)
http://dx.doi.org/10.1038/nn1489 [view abstract]
Stimuli can be discriminated without being consciously perceived and can be preferred without being remembered. Here we report a subject with a previously unknown dissociation of abilities: a strong behavioral preference for the taste of sugar over saline, despite a complete failure of recognition. The pattern of brain damage responsible for the dissociation suggests that reliable behavioral choice among tastes can occur in the absence of the gustatory cortex necessary for taste recognition.
Bijal P. Trivedi
http://dx.doi.org/10.1038/486S7a [view abstract]
Research into human taste receptors extends beyond the tongue to some unexpected places.
N-C Liang, N T Bello, T H Moran
International Journal of Obesity (2012)
http://dx.doi.org/10.1038/ijo.2012.16 [view abstract]
One developing strategy for obesity treatment has been to use combinations of differently acting pharmacotherapies to improve weight loss with fewer adverse effects. The purpose of this study was to determine whether the combination of naltrexone (Nal), an opioid antagonist acting on the reward system, and exendin-4 (Ex-4), a glucagon-like peptide 1 agonist acting on satiety signaling, would produce larger reductions in food intake than either alone in rats. Because the anorectic potencies of both compounds have been associated with nausea and malaise, the influence of these drug combinations on the acquisition of a conditioned taste aversion (CTA) was also determined. In Experiment 1, the acute anorectic effects of Nal (0.32–3.2 mg kg−1; intraperitoneally (i.p.)) and Ex-4 (1–10 μg kg−1; i.p.) were assessed alone or in combination. Combinational doses were further investigated by the repeated daily administration of 1 mg kg−1 Nal+3.2 μg kg−1 Ex-4 for 4 days. In Experiment 2, both compounds alone or in combination were used as unconditioned stimuli in a series of CTA tests. Nal and Ex-4, alone or in combination, suppressed food intake in a dose-dependent manner, and the interaction on food intake between Nal and Ex-4 was additive. In the CTA paradigm, Nal (1 mg kg−1) alone did not support acquisition, whereas a CTA was evident with doses of Ex-4 (1 or 3.2 μg kg−1). Combinations of Nal and Ex-4 also resulted in a more rapid and robust acquisition of a CTA. Given that the Nal and Ex-4 combination produces additive effects on not only food intake reduction but also food aversion learning, this specific drug combination does not have the benefit of minimizing the adverse effects associated with each individual drug. These data suggest that it is necessary to evaluate both the positive and adverse effects at early stages of combinational drug development.
One developing strategy for obesity treatment has been to use combinations of differently acting pharmacotherapies to improve weight loss with fewer adverse effects. The purpose of this study was to determine whether the combination of naltrexone (Nal), an opioid antagonist acting on the reward system, and exendin-4 (Ex-4), a glucagon-like peptide 1 agonist acting on satiety signaling, would produce larger reductions in food intake than either alone in rats. Because the anorectic potencies of both compounds have been associated with nausea and malaise, the influence of these drug combinations on the acquisition of a conditioned taste aversion (CTA) was also determined.METHODS:
In Experiment 1, the acute anorectic effects of Nal (0.32–3.2 mg kg−1; intraperitoneally (i.p.)) and Ex-4 (1–10 μg kg−1; i.p.) were assessed alone or in combination. Combinational doses were further investigated by the repeated daily administration of 1 mg kg−1 Nal+3.2 μg kg−1 Ex-4 for 4 days. In Experiment 2, both compounds alone or in combination were used as unconditioned stimuli in a series of CTA tests.RESULTS:
Nal and Ex-4, alone or in combination, suppressed food intake in a dose-dependent manner, and the interaction on food intake between Nal and Ex-4 was additive. In the CTA paradigm, Nal (1 mg kg−1) alone did not support acquisition, whereas a CTA was evident with doses of Ex-4 (1 or 3.2 μg kg−1). Combinations of Nal and Ex-4 also resulted in a more rapid and robust acquisition of a CTA.CONCLUSION:
Given that the Nal and Ex-4 combination produces additive effects on not only food intake reduction but also food aversion learning, this specific drug combination does not have the benefit of minimizing the adverse effects associated with each individual drug. These data suggest that it is necessary to evaluate both the positive and adverse effects at early stages of combinational drug development.
http://dx.doi.org/10.1038/1811472a0 [view abstract]
In an endeavour to establish whether such changes in the significance of the afferent neural message are related to changes in taste sensitivity I have twice rendered a man and a woman deficient in salt, and studied their sensitivity to solutions in distilled water of sodium chloride, sucrose, sulphuric acid and quinine sulphate (chemicals supplied by B.D.H.,Ltd.). The psychophysical method of limits, ascending series only, was used to establish absolute thresholds. The series of concentrations (grams of solute per 100 cm.3 of solution) of the salt, sweet and sour solutions were graded in steps of 0 -05 of a logarithmic unit, the bitter solutions in steps of 0-1 of a logarithmic unit.
International Journal of Obesity (2005)
http://dx.doi.org/10.1038/sj.ijo.0803082 [view abstract]
Jean C Burge, Hi Sung Park, Carole P Whitlock, Rachel A Schemmel
Kidney International (1979)
http://dx.doi.org/10.1038/ki.1979.7 [view abstract]
Taste acuity in patients undergoing long-term hemodialysis. Recognition taste thresholds for the four primary tastes, sour, sweet, salty, and bitter, were determined in 18 patients (age range, 17 to 65 years) with end-stage kidney disease and were compared to 10 age and sex matched controls. In experimental subjects, mean taste thresholds before and after dialysis for tartaric acid were 0.004 N and 0.002 N, respectively, compared to 0.0002 N for controls. For sucrose, before and after dialysis, mean taste thresholds were 0.039 M and 0.023 M, respectively, and 0.014 M for controls. When we used the same taste modalities, that is, sweet or sour, all possible comparisons were significant except the one for sweet between patients after dialysis and controls. Mean recognition taste thresholds for salty and bitter were not significantly impaired in dialysis patients when compared to controls. Mean serum zinc concentrations were 77 µg/dl, both before and after dialysis. Since these are low-normal values, zinc could be a contributing factor in loss of taste among these patients, but it can't explain the improvement seen in taste acuity associated with dialysis for 6 to 8 hours. Since taste acuity improved with dialysis, it is conceivable that recognition taste thresholds could be adapted so that they could complement or substitute for the current serum urea kinetics calculations used in many programs to assess the adequacy of dialysis.
Bernd Bufe, Thomas Hofmann, Dietmar Krautwurst, Jan-Dirk Raguse, Wolfgang Meyerhof
Nature Genetics (2002)
http://dx.doi.org/10.1038/ng1014 [view abstract]
Bitter taste generally causes aversion, which protects humans from ingesting toxic substances. But bitter flavors also contribute to the palatability of food and beverages, thereby influencing nutritional habits in humans. Although many studies have examined bitter taste, the underlying receptor mechanisms remain poorly understood. Anatomical, functional and genetic data from rodents suggest the existence of a family of receptors that are responsive to bitter compounds. Here we report that a human member of this family, TAS2R16, is present in taste receptor cells on the tongue and is activated by bitter β-glucopyranosides. Responses to these phytonutrients show a similar concentration dependence and desensitization in transfected cells and in experiments assessing taste perception in humans. Bitter compounds consisting of a hydrophobic residue attached to glucose by a β-glycosidic bond activate TAS2R16. Thus, TAS2R16 links the recognition of a specific chemical structure to the perception of bitter taste. If the ability of TAS2R16 to detect substances with common molecular properties is typical of the bitter receptor family, it may explain how a few receptors permit the perception of numerous bitter substances.
S C Benoit, R J Sheldon, E L Air, P Messerschmidt, K A Wilmer, K M B Hodge, M B Jones, D M M Eckstein, C C McOsker, S C Woods, R J Seeley
International Journal of Obesity (2003)
http://dx.doi.org/10.1038/sj.ijo.0802280 [view abstract]
BACKGROUND: The synthetic melanocortin (MC) agonist, melanotan-II (MTII), reduces food intake and body weight for hours to days after administration. One early report on the effect of MTII suggested that part of its anorexic action may be mediated by aversive consequences. In that experiment, MTII was found to support a mild conditioned taste aversion (CTA).
OBJECTIVE: The present experiments replicate and extend those findings in two additional CTA paradigms to further characterize the aversive effects of MTII in rats.
METHODS: Experiment 1 simultaneously assessed the ability of MTII to support CTA and reduce food intake, using a small oral infusion of a novel taste as the conditioned stimulus. Experiment 2 assessed the aversive consequences of chronic MTII administration. To accomplish this, we paired implantation of lithium chloride (LiCl)-, MTII- or saline-containing osmotic minipumps with a constantly available novel flavor. After 7 days, rats received a choice test between the minipump-paired flavor and a previously available neutral flavor.
RESULTS: Rats with saline minipumps exhibited no preference for either flavor. By contrast, rats in both the LiCl and MTII minipump groups significantly preferred the neutral flavor, indicating the development of a CTA. Additionally, CTA produced by administration of MTII was found to be more resistant to extinction than that produced by LiCl.
CONCLUSIONS: The reduction in food intake caused by MTII is accompanied by aversive consequences regardless of route of administration. These results present difficulties for the development of MCs-based therapies for obesity.
Ying-Ying He, Yan-Xue Xue, Ji-shi Wang, Qin Fang, Jian-Feng Liu, Li-Fen Xue, Lin Lu
http://dx.doi.org/10.1038/npp.2011.63 [view abstract]
The intense associative memories that develop between drug-paired contextual cues and rewarding stimuli or the drug withdrawal-associated aversive feeling have been suggested to contribute to the high rate of relapse. Various studies have elucidated the mechanisms underlying the formation and expression of drug-related cue memories, but how this mechanism is maintained is unknown. Protein kinase M ζ (PKMζ) was recently shown to be necessary and sufficient for long-term potentiation maintenance and memory storage. In the present study, we used conditioned place preference (CPP) and aversion (CPA) to examine whether PKMζ maintains both morphine-associated reward memory and morphine withdrawal-associated aversive memory in the basolateral amygdala (BLA). We also investigate the role of PKMζ in the infralimbic cortex in the extinction memory of morphine reward-related cues and morphine withdrawal-related aversive cues. We found that intra-BLA but not central nucleus of the amygdala injection of the selective PKMζ inhibitor ZIP 1 day after CPP and CPA training impaired the expression of CPP and CPA 1 day later, and the effect of ZIP on memory lasted at least 2 weeks. Inhibiting PKMζ activity in the infralimbic cortex, but not prelimbic cortex, disrupted the expression of the extinction memory of CPP and CPA. These results indicate that PKMζ in the BLA is required for the maintenance of associative morphine reward memory and morphine withdrawal-associated aversion memory, and PKMζ in the infralimbic cortex is required for the maintenance of extinction memory of morphine reward-related cues and morphine withdrawal-related aversive cues.
Gert Jansen, David Weinkove, Ronald H.A. Plasterk
The EMBO Journal (2002)
http://dx.doi.org/10.1093/emboj/21.5.986 [view abstract]
Caenorhabditis elegans has two heterotrimeric G-protein γ subunits, gpc-1 and gpc-2. Although GPC-1 is specifically expressed in sensory neurons, it is not essential for the detection of odorants or salts. To test whether GPC-1 is involved in sensory plasticity, we developed a water soluble compound adaptation assay. The behaviour of wild-type animals in this assay confirms that prolonged exposure to salts can abolish chemo-attraction to these compounds. This process is time and concentration dependent, partly salt specific and reversible. In contrast, gpc-1 mutant animals show clear deficits in their ability to adapt to NaAc, NaCl and NH4Cl, but normal wild-type adaptation to odorants. Two other loci previously implicated in odorant adaptation, adp-1 and osm-9, are also involved in adaptation to salts. Our finding that G proteins, OSM-9 and ADP-1 are involved in taste adaptation offer the first molecular insight into this process.
JB Epstein, N Phillips, J Parry, MS Epstein, T Nevill, P Stevenson-Moore
Bone Marrow Transplantation (2002)
http://dx.doi.org/10.1038/sj.bmt.1703716 [view abstract]
Multiple oral complaints develop following high-dose chemo/radiotherapy and hematopoietic cell transplantation (HCT) which can influence quality of life. The purpose of this investigation was to assess quality of life, oral function, taste and smell in a cohort of patients following HCT. A general quality of life survey (the European Organization for Research and Treatment of Cancer (EORTC)) Quality of Life (QOL) questionnaire (QLQ-C30), with an added oral symptom and function scale and assessment of taste and smell was administered to a consecutive series of patients at day 90–100 post HCT. General QOL was impacted by fatigue, affecting physical, social emotional and cognitive function. While oral function scales appeared to be little affected at day 90–100 post HCT, abnormalities of taste were reported. Reports of changes in taste and smell appeared to parallel each other and changes remained at the time of the survey post-HCT. Change in taste appeared to be closely associated with dry mouth. Patients appeared to have difficulty in differentiating sour and bitter, which had been more affected than salt and sweet taste. Females appeared to report greater changes in taste than males. Increased smell sensitivity and taste change resulted in changes in food preparation in some cases, as did reported increase in sensitivity to sour and bitter taste. Acute complications are well known to affect QOL during the early period following HCT, but little assessment of long-term changes in oral QOL and taste has been conducted following transplant. The EORTC QLQ C-30 questionnaire with the oral addendum provides a measure of the quality of life and oral function, and may provide useful outcome measures for assessment of oral care prevention and management in HCT patients.