Aversive Taste Stimuli Research Articles

Involvement of forebrain in parabrachial neuronal activation induced by aversively conditioned taste stimuli in the rat

We previously have shown that forebrain inputs increase responses of amiloride-sensitive NaCl-best neurons to the conditioned stimulus (CS) in the rat parabrachial nucleus (PBN) after the establishment of conditioned taste aversion (CTA) to NaCl. In the present study, we examined the effects of aversively-conditioned NaCl taste stimulation on Fos-like immunoreactivity (FLI) in the PBN using awake intact and decerebrate rats. In Experiment 1, the CTA-trained and sham-conditioned control rats were intraorally infused with 0.1 M NaCl or 0.1 M NaCl mixed with 10 − 4 M amiloride, a sodium-channel blocker. Significantly more NaCl-stimulated FLI was observed in the central medial (cms) and external lateral subnuclei (els) of PBN in the CTA-trained group than in the control group. In both groups, amiloride markedly reduced NaCl-stimulated FLI in the cms but not in the els. In Experiment 2, we found that after decerebration, there was no significant difference in FLI between the CTA-trained and sham-conditioned groups. These results suggest that (1) amirolide-sensitive taste information of NaCl projects mainly to the cms; (2) sensory information of aversive taste stimuli is likely to be represented in the els; and (3) forebrain inputs are required for elevated FLI in the PBN after CTA.

The Neuroscience of Pleasure. Focus on “Ventral Pallidum Firing Codes Hedonic Reward: When a Bad Taste Turns Good”

For more than 2,000 years, philosophers have struggled to define, let alone explain, pleasure or hedonics. With contemporary animal models and techniques, scientists now have the ability to provide a comprehensive description of this affective state by examining its neural underpinnings. In this issue of the Journal of Neurophysiology (p. 2399 –2409), Tindell and colleagues use an elegant, reductionist approach to take a profound step in defining these neural foundations (Tindell 2006). The authors control for various elements of reward that historically have confounded researchers ambitious enough to attempt to study such an intangible topic. Specifically, Tindell and colleagues establish a role for ventral pallidum (VP) neurons in encoding hedonics. The authors infused an unpalatable concentration of saline into the oral cavities of rats while recording the extracellular electrophysiological activity of single VP neurons. Aversive orofacial reactions to the unpalatable taste were simultaneously measured. Three days later, rats were made sodium deplete and retested. In a sodium-depleted state, these rats now exhibited a behavioral switch from aversive taste reactivity to appetitive taste reactivity coincident with increased VP activity to the infusion of saline (similar to responses for a palatable sucrose solution). The clever implicit controls indicate that the altered electrophysiological activity encodes a hedonic shift rather than alterations in motivated behavior or sensory coding.

Modulation of human cortical swallowing motor pathways after pleasant and aversive taste stimuli

Human swallowing involves the integration of sensorimotor information with complexities such as taste; however, the interaction between the taste of food and its effects on swallowing control remains unknown. We assessed the effects of pleasant (sweet) and aversive (bitter) tastes on human cortical swallowing motor pathway excitability. Healthy adult male volunteers underwent a transcranial magnetic stimulation (TMS) mapping study (n = 9, mean age: 34 yr) to assess corticobulbar excitability before and up to 60 min after 10-min liquid infusions either 1) as swallowing tasks or 2) delivered directly into the stomach. Infusions were composed of sterile water (neutral), 10% glucose (sweet), and 0.5 mM quinine hydrochloride (bitter). The order of delivery was randomized, and each infusion was given on separate days. Pharyngeal motor-evoked potentials (PMEPs) were recorded from an intraluminal catheter as a measure of corticobulbar excitability and compared using repeated-measures and one-way ANOVA. After the swallowing task (water, glucose, or quinine), repeated-measures ANOVA revealed a significant time interaction across tastants (P </= 0.01). One-way ANOVA for each taste showed changes in PMEP amplitudes for both quinine (P </= 0.001) and glucose (P </= 0.009) solutions but not for water (P = 0.1). Subsequent t-tests showed that glucose and quinine reduced PMEPs by 47% (SD 34) and 37% (SD 54), respectively, at 30 min (P </= 0.03). No changes were observed after the infusion of any solution directly into the stomach (P = 0.51). In conclusion, cortical swallowing pathways are similarly modulated by both sweet and bitter tasting stimuli. Changes likely reflect a close interaction between taste and swallowing activity mediated in the central nervous system.

Nucleus Accumbens Neurons Are Innately Tuned for Rewarding and Aversive Taste Stimuli, Encode Their Predictors, and Are Linked to Motor Output

The nucleus accumbens (NAc) is a key component of the brain's reward pathway, yet little is known of how NAc cells respond to primary rewarding or aversive stimuli. Here, naive rats received brief intraoral infusions of sucrose and quinine paired with cues in a classical conditioning paradigm while the electrophysiological activity of individual NAc neurons was recorded. NAc neurons (102) were typically inhibited by sucrose (39 of 52, 75%) or excited by quinine (30 of 40, 75%) infusions. Changes in firing rate were correlated with the oromotor response to intraoral infusions. Most taste-responsive neurons responded to only one of the stimuli. NAc neurons developed responses to the cues paired with sucrose and quinine. Thus, NAc neurons are innately tuned to rewarding and aversive stimuli and rapidly develop responses to predictive cues. The results indicate that the output of the NAc is very different when rats taste rewarding versus aversive stimuli.

Nucleus Accumbens Neurons Are Innately Tuned for Rewarding and Aversive Taste Stimuli, Encode Their Predictors, and Are Linked to Motor Output

Nucleus Accumbens Neurons Are Innately Tuned for Rewarding and Aversive Taste Stimuli, Encode Their Predictors, and Are Linked to Motor Output

Representation of Taste Stimuli in the Brain

Ingestive behavior is controlled by various neural systems in the central nervous system such as oromotor and taste neural systems. Since the taste system is the final arbiter by which an animal determines whether a chemical or food will be acceptable (Travers and Norgren, 1986), the taste system is one of the main neural systems for ingestive behavior. The brainstem contains a basic neural system for ingestive behavior, that includes brainstem taste areas such as the nucleus of the solitary tract (NTS) and the pontine parabrachial nucleus (PBN), by which the animal can manifest different oromotor responses to four basic tastes (Grill and Norgren, 1978). It has been suggested that the forebrain, including the amygdala (AM) and hypothalamus, which receives taste information from the brainstem taste areas, is a higher center which modulates activity of this basic neural system by its descending projections (Norgren, 1995). The AM and hypothalamus, which receives massive afferent fibers from the AM, have been reported to be important in motivation, feeding behavior and evaluation of the biological significance of sensory stimuli (Rolls, 1976; Nishijo et al., 1988). Lesions of the AM and hypothalamus altered food preference in monkeys and rats (Murray et al., 1996; Isaacson, 1982) and attenuated behavioral responses to both preferred and aversive taste stimuli in rats (Kemble and Schwartzbaum, 1969). Furthermore, decerebration and electrical stimulation or inactivation of the forebrain modulated activity of taste neurons in the NTS and PBN (Matsuo et al., 1984; Mark et al., 1988; Di Lorenzo, 1990). In the present study, to investigate the nature of taste information processing in the AM, neuronal activity was recorded from the AM during discrimination of sensory stimuli associated with various taste solutions and ingestion of taste solutions.

Effects of pleasant and aversive taste stimuli on the excitability of healthy human cortico-bulbar swallowing motor pathways

Effects of pleasant and aversive taste stimuli on the excitability of healthy human cortico-bulbar swallowing motor pathways

Differential Expression of Motivational Stimulus Properties by Dopamine in Nucleus Accumbens Shell versus Core and Prefrontal Cortex.

The response of extracellular dopamine (DA) and its relationship to motivational valence (positive or negative) and novelty of motivational stimuli was investigated by brain microdialysis in the nucleus accumbens (NAc) shell and core and prefrontal cortex (PFCX) of rats. Stimuli were elicited by intraoral infusion of 20% sucrose, sucrose plus chocolate, quinine, and NaCl solutions, feeding of a palatable food (Fonzies), or smelling of a predator (red fox) urine. Sucrose elicited appetitive reactions and increased DA in the PFCX but not in the NAc shell. An unfamiliar appetitive taste such as that of sweet chocolate and Fonzies, increased DA in all three areas. Habituation of the stimulatory DA response to intraoral chocolate or to Fonzies feeding was observed in the NAc shell after a single pre-exposure to the same taste or food; no habituation was observed in the NAc core nor in the PFCX. Aversive taste stimuli (quinine, saturated NaCl solutions) rapidly increased DA in the PFCX and in the NAc core, and this response did not undergo one-trial habituation. In the NAc shell, instead, no effect (10 min exposure) or a delayed, transitory increase of DA (5 min exposure) sensitive to one-trial habituation was obtained in response to the aversive taste (quinine and saturated NaCl) or olfactory (red fox urine) stimuli. These observations indicate that DA responsiveness is an integrated function of the motivational valence and novelty of stimuli in the NAc shell and an expression of generic motivational value in the NAc core and PFCX.

Differential Expression of Motivational Stimulus Properties by Dopamine in Nucleus Accumbens Shell versus Core and Prefrontal Cortex

The response of extracellular dopamine (DA) and its relationship to motivational valence (positive or negative) and novelty of motivational stimuli was investigated by brain microdialysis in the nucleus accumbens (NAc) shell and core and prefrontal cortex (PFCX) of rats. Stimuli were elicited by intraoral infusion of 20% sucrose, sucrose plus chocolate, quinine, and NaCl solutions, feeding of a palatable food (Fonzies), or smelling of a predator (red fox) urine. Sucrose elicited appetitive reactions and increased DA in the PFCX but not in the NAc shell. An unfamiliar appetitive taste such as that of sweet chocolate and Fonzies, increased DA in all three areas. Habituation of the stimulatory DA response to intraoral chocolate or to Fonzies feeding was observed in the NAc shell after a single pre-exposure to the same taste or food; no habituation was observed in the NAc core nor in the PFCX. Aversive taste stimuli (quinine, saturated NaCl solutions) rapidly increased DA in the PFCX and in the NAc core, and this response did not undergo one-trial habituation. In the NAc shell, instead, no effect (10 min exposure) or a delayed, transitory increase of DA (5 min exposure) sensitive to one-trial habituation was obtained in response to the aversive taste (quinine and saturated NaCl) or olfactory (red fox urine) stimuli. These observations indicate that DA responsiveness is an integrated function of the motivational valence and novelty of stimuli in the NAc shell and an expression of generic motivational value in the NAc core and PFCX.

Diazepam-binding inhibitor-like activity in rat cerebrospinal fluid after stimulation by an aversive quinine taste.

Cerebrospinal fluid (CSF) taken from rats after stimulation by an aversive quinine taste (hereafter called quinine CSF) administered into the fourth ventricle of mice suppressed their intake of 5% sucrose solution. We examined the effects of CSF on glutathione-induced tentacle ball formation (TBF) of hydra to determine the change in CSF components associated with aversive taste stimuli. The suppressive activity of quinine CSF on TBF in the presence of 3 microM S:-methyl-glutathione (GSM) was markedly lower than that of CSF obtained from control rats (control CSF). Pronase-treated quinine CSF had suppressive activity similar to that of control CSF. The active principle passed through an ultrafiltration membrane, with a molecular weight cut-off of 30 kDa, but not through one with a cut-off of 3 kDa. A peptide fragment of diazepam-binding inhibitor (DBI) nullified the suppression of TBF at 3 microM GSM by control CSF. The nullifying activity of quinine CSF was not observed after treatment with a benzodiazepine receptor preparation that was able to bind DBI. When flumazenil, a benzodiazepine receptor antagonist, was given to mice, the suppression of the intake of 5% sucrose solution by quinine CSF was partially reversed. It is suggested that quinine CSF contains a DBI-like substance.

How do inositol and glucose modulate feeding in Manduca sexta caterpillars?

Many species of caterpillar possess taste cells that respond exceptionally vigorously to the sugar alcohol myo-inositol. We examined the functional significance of these inositol-sensitive taste cells in Manduca sexta caterpillars through an integrated series of electrophysiological and behavioral studies. Neural recordings from all the gustatory chemosensilla revealed that M. sexta have only two pairs of inositol-sensitive taste cells, which respond strongly and selectively to myo-inositol, and two pairs of sugar-sensitive taste cells, which respond relatively weakly to sugars (glucose and sucrose). Behavioral studies established that myo-inositol incites feeding and counteracts the inhibitory effects of aversive taste stimuli (e.g. caffeine) on feeding, but does not promote increased consumption once feeding has been initiated. In contrast, glucose and sucrose did not produce any robust effects on feeding. We failed to obtain any evidence of sensory inhibition between taste cells that responded to myo-inositol and caffeine, indicating that myo-inositol counteracts the inhibitory effects of caffeine on feeding through a central gustatory mechanism. We conclude that sensory input from the inositol-sensitive taste cells, but not the sugar-sensitive taste cells, plays an important role in regulating feeding in M. sexta.

Conditioned reflex responses of the sympathetico-adrenal system to an aversive taste stimulus.

Studies were carried out on male and female rats in which the effects of isolated presentation of a conditioned stimulus (a saccharine solution) to which the animals had previously developed conditioned reflex taste aversion (RTA) on the level of urinary catecholamine secretion were determined. The studies showed that presentation of an aversive taste stimulus without reinforcement by a negative stimulus increased the levels of urinary adrenaline, noradrenaline, and dopamine secretion; this repeated, albeit more weakly, the effects of the negative reinforcement (angular acceleration) used for development of RTA. After presentation of the isolated aversive taste stimulus, the greatest increase in catecholamine excretion affected adrenaline, which indicates an anxiety state (fear). There was also a significant increase in noradrenaline excretion in these conditions. The accompanying increase in dopamine excretion in experimental and control animals showed this change to be largely nonspecific in nature, and to result from the experimental procedures. Isolated presentation of the conditioned taste stimulus elicited significantly greater increases in urinary catecholamine excretion in males than in females. It is suggested that the time for which the RTA is retained could be increased by activation of the sympathetico-adrenal system resulting from presentation of the nonreinforced taste stimulus which had acquired aversive properties.

Aversive taste stimuli facilitate extracellular acetylcholine release in the insular gustatory cortex of the rat: a microdialysis study

The release of extracellular acetylcholine (ACh) in the insular gustatory cortex of conscious rats during taste stimulation was measured using the microdialysis technique. The mean basal release of ACh before stimulation was 273 ± 21 fmol/10 μl (mean ± S.E.M., n = 25). Intraorally applied taste stimuli or distilled water significantly increased the release of ACh. Among them, infusion of 0.001 M quinine HCl produced a marked increase in the release of ACh up to 355% of baseline levels. Infusion of 0.01 M saccharin to the subjects that had acquired an aversion to this taste also caused a prominent increase in ACh up to 343% of basal levels. In contrast, saccharin infusion to the naive subjects moderately increased ACh up to 243% of baseline. Water infusion resulted in the smallest increase in ACh up to 175% of baseline. Although intraoral infusions of quinine or distilled water caused a significant increase in ACh in the parietal cortex, the magnitude of increased ACh was smaller than that in the gustatory cortex. These results suggest that ACh release in the insular gustatory cortex is related to behavioral expression to aversive taste stimuli.

Gustatory control of feeding behavior in goldfish

The present study tests the effects of gustatory quality on feeding behaviors exhibited by goldfish. Goldfish were trained to feed on gelatin pellets, then tested with pellets containing potentially aversive taste stimuli (quinine or caffeine), or mixtures of aversive and appetitive components (amino acids or food). Goldfish feeding includes: initial intake of food particles, a sorting phase consisting of rinsing and backwashing, and a final phase terminating in either rejection or ingestion. Pellets flavored with quinine or caffeine were rejected at concentrations above 10 −5 and 10 −3 M, respectively. Pellets containing a mixture of quinine and ground food or quinine and either l-alanine or l-proline were ingested more frequently than pellets flavored only with quinine. These pellets with mixed chemical components also produced extended sorting behaviors, including prolonged periods of rinsing and backwashing. The prolonged sorting of quinine-food mixtures enabled the animals to separate mechanically the food from the gelatin matrix. These results show that goldfish use chemical cues to drive the intraoral sorting and rejection/ingestion behaviors.

Development of Altered Taste Preferences in Tumor-bearing Rats

Experimental tumors induce a decline in food intake that may derive from changes in taste or the development of taste aversions. The preferences of tumor-bearing (TB) and non-tumor-bearing (NTB) rats for five chemicals (three palatable and two aversive taste stimuli) were studied in an animal model of experimental cancer employing the methylcholanthrene (MCA) sarcoma. In protocol 1, five groups of Fischer 344 rats were given 23-h, two-bottle preference tests (taste solution vs. water) daily from day 3 after tumor implantation until spontaneous death occurred. Both NTB and TB rats avoided quinine hydrochloride and hydrochloric acid solutions throughout the experiment indicating that tumor growth produced no disruption in the animals' perception of these normally aversive tastes. In both groups, preference for sucrose (88% to 97%) and saccharin (75% to 93%) remained high until days 22 and 17 respectively, but tended to decline with advanced tumor growth. In both cases, a reduction in total calorie intake preceded the changes in sucrose or saccharin preference by several days. With or without a tumor, rats exhibited approximately 50% preference for NaCl at all times. In protocol 2, a four-bottle preference test (sucrose vs. saccharin vs. NaCl vs. water) was administered before tumor implantation and again 3 weeks later when a decline in food intake was evident. Both TB and NTB rats displayed a dominant preference for sucrose over saccharin, NaCl, and water at the pre- and posttests. However, a comparison of the difference scores (pre- minus postimplantation) of NTB and TB rats showed a small but significant suppression of TB animals' preference for sucrose. The altered preferences for sweet but not salt taste stimuli suggest that food-related taste cues may be more susceptible to the development of taste aversions during cancer. However the contribution of taste changes to the anorexia of cancer remains unclear and it is possible that the changes in taste preference may be secondary to the reduction in food intake.

Aversive taste stimuli increase CGRP levels in the gustatory insular cortex of the rat

Calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) was surveyed immunohistochemically in the insular cortex of the rat, and the levels of insular cortical CGRP-IR were measured with the radioimmunoassay method following intraoral stimulation with various taste stimuli. CGRP-IR was localized in nerve fibers within the agranular and dysgranular insular cortices. The CGRP-IR levels in the rostral (gustatory) part of the insular cortex were increased significantly by strongly aversive taste stimuli such as quinine hydrochloride and conditioned taste stimuli (NaCl and sucrose) which animals had been taught to avoid. The results suggest that CGRP in the gustatory insular cortex is concerned with rejection or avoidance behaviors to aversive taste stimuli.

Self-selection of dietary threonine in the rat and the effect of taste stimuli on its selection.

The possible regulation of dietary threonine intake and the effect of a palatable (sodium saccharin) or aversive (quinine sulfate) taste stimulus on the manner of threonine selection were investigated in rats using a self-selection feeding method. Weanling rats were offered the choice of two diets differing only in threonine content for 2 weeks. Both weight gain and food consumption in the rats offered the choice of diets were quite comparable to each other and were the same as those in rats fed one diet containing sufficient threonine. Threonine intake of the self-selecting rats ranged from 0.43 to 1.90% of the food consumed. The threonine concentrations in the plasma and brain of the self-selecting rats increased proportionally with the threonine intake. When rats were offered a choice of two diets containing various amounts of threonine with taste materials, i.e., sodium saccharin or quinine sulfate, neither the dietary threonine nor their growth were ever affected.These results indicate clearly that r...

Rumination in infancy: Recent behavioral approaches

The published literature on behavioral treatments of rumination is reviewed, and new case material on two recently reported procedures is presented. Rumination, a medical condition of infancy involving repeated regurgitation of previously ingested food, has historically been treated from a psychodynamic approach involving extended in-patient treatment by mother surrogates. This procedure is both time-consuming and very costly. The initial behavioral approach involved electric shock. Single-case studies reflect the utility of this procedure, but widespread resistance to this form of punishment makes this a difficult procedure to utilize. More recent behavioral procedures reported in single-case studies have included delivering aversive taste stimuli as consequences for ruminating. This procedure has met with mixed success, and has the added drawback of being difficult to implement technically and because of staff resistance. A combination of punishment by scolding, time-out, and reinforcement of retaining the food constitutes a useful alternative. This procedure has the added advantage of being more acceptable to staff and implementable at home. The possibility of individual differences among ruminators that might predict success is also raised.

Effects of unpalatable diets and food restriction on feed efficiency in growing rats

During a 15-day experiment, weanling rats fed a 10% casein diet adulterated daily by one of four aversive taste stimuli ate 12–16% less than their controls fed ad lib on the unadulterated diet. They also demonstrated an inhibition in feed efficiency (g body weight gain/g food intake) during the first 8 days. A second control group, pair-fed to the group receiving the adulterated diet, also showed a reduction in feed efficiency. By Day 9, a compensatory process was evident in the rats fed the unpalatable diet such that feed efficiency increased above that observed for the ad lib control group. By the end of the experiment all three groups exhibited the same efficiency. The ratio of urinary nitrogen to total nitrogen intake was higher in rats fed the unpalatable diet ad lib compared to those offered the unadulterated diet ad lib. This observation suggests that the rats on the unpalatable diet were using more of the dietary protein as a caloric source than were their controls.

Diet palatability and growth efficiency: Evidence for a physiological interrelationship in rats

The total food intake and growth efficiency of growing rats were not affected by the feeding of a mild protein restricted (10%) diet containing an aversive taste stimulus. However, growing rats fed the same diet for a period of 18 days, suffered an inhibition of growth efficiency if the taste character of the diet was changed daily by the addition of a single but different aversive stimulus. For a period of time (9 days), these changes in diet palatability did not affect the total food intake. Rats fed diets containing a combination of the aversive taste changes and commercial soybean trypsin inhibitors, suffered an additional inhibition of growth efficiency. It is postulated that these manipulations in diet palatability interfered with digestive or metabolic processes.