Quinine Solution Research Articles

Taste preference and acceptance in thirsty and dehydrated rats

Experiments were designed to determine whether water deprivation affects taste preferences and/or taste acceptance. In experiment 1, both five- and two-bottle preference tests were performed in normally hydrated rats to permit the selection of five groups of rats showing the same taste preference for one of four prototypical tastes. Subsequently, in the same groups of rats, taste preferences were determined by a two-bottle test (experiment 2), and taste acceptance by a one-bottle test (experiment 3), following 12, 24, 36, and 48 h of water deprivation. After both 12 and 24 h of dehydration, during the first 10 min of the tests of experiment 2, all rats ingested greater volumes of either NaCl or sucrose solution than water, but more water than either HCl or quinine solution, and the differences were very significant ( P<.0001). After 36 or 48 h of dehydration, the differences became very small and, in some cases, the P-values were at the lowest or borderline level of the significance, suggesting that dehydrated rats poorly discriminate the nature of the fluid drunk. During the 11–60 min interval, all rats preferred either sucrose or NaCl to water, but water to either HCl or quinine. Experiment 3 was performed to ascertain whether the need for fluid might overcome the palatability of solutions. All rats, dehydrated for 36 or 48 h, after 10 min of exposure, drank equal amounts of fluid, independent of its palatability. During the 11–20 and 21–60 min interval, the fluid intake of rats changed in accordance with the palatability of the solution available. In conclusion, severe thirst in rats may override the palatability of the solutions, and the thirst drive may be so strong that they do not reject fluids because body fluid balance would be severely compromised.

Bitter and sweet components of ethanol taste in humans

This study examined taste descriptions elicited by ethanol and by other tastants in humans. All subjects described 10% ethanol as bitter and ≈30% of the subjects described it as sweet and/or sour. Highly significant correlations were found between sweetness of some sucrose solutions (0.6–1%) and intensity of the taste of ethanol. In another experiment, quinine (bitter) solutions were rated as similar to 10% ethanol taste and this effect was potentiated by the addition of sucrose. In contrast, citric acid (sour) tended to decrease similarity ratings when added to the quinine solutions. Taken together, these findings suggest that: (1) in humans ethanol tastes both bitter and sweet; and (2) the relationship between sucrose and ethanol intakes previously found in animals and humans may result, at least partially, from similar taste responses elicited by sucrose and ethanol.

The effects of cAMP on the excitability and responses of defensive behavior command neurons in the common snail evoked by sensory stimuli.

Experiments on snails showed that extracellular application of dibutyryl-cAMP (db-cAMP) or intracellular application of cAMP for 30 min evoked increases in excitability and synaptic facilitation in responses to sensory stimulation of defensive behavior command neurons LP11 and RP11. Excitability increased 45-60 min after the start of addition of db-cAMP or cAMP and remained elevated until the end of the experiment (3-4 h). Synaptic facilitation started 50-60 min after the onset of extracellular application of db-cAMP and remained detectable in the responses of neurons to tactile stimulation of the head for 1 h and to application of dilute quinine solution for 2-4 h. Application of db-cAMP produced no changes in responses to tactile stimulation of the foot or mantle ridge. Intracellular injection of cAMP induced facilitation of neuron responses only to weak quinine solutions. The responses of neurons to tactile stimulation of the head, foot, and mantle ridge did not change after injections of cAMP. It is suggested that cAMP is involved in the mechanisms controlling the excitability of neurons LP11 and RP11. In addition, cAMP is selectively involved in the postsynaptic mechanism inducing the transient stage of long-term facilitation of synaptic "inputs," which mediates excitation evoked by chemical stimuli. This set of effects of cAMP is similar to effects arising during the development of nociceptive sensitization and in response to serotonin.

Effects of taste stimulation on β-endorphin levels in rat cerebrospinal fluid and plasma

Opioids are suggested to be involved in generation of palatability and facilitation of consumption of food and fluid. We measured the level of an endogenous opioid, β-endorphin, in the cerebrospinal fluid (CSF) and plasma after free drinking of water and taste solutions in Wistar rats. When the water-deprived animals were allowed to drink 10 mL of water, the level of β-endorphin increased significantly 60 and 90 min after the start of drinking in both samples. β-Endorphin in the CSF increased most after ingestion of 0.5 M sucrose and 0.005 M saccharin followed by 0.1 M NaCl, 0.1 mM quinine and water. An intragastric infusion of 7 mL of water did not change the β-endorphin level. Essentially the same results were obtained for plasma samples except that NaCl and quinine solutions did not increase β-endorphin levels. Sucrose became ineffective in releasing β-endorphin in both samples after the establishment of conditioned taste aversions to this taste stimulus. These results suggest that the release of β-endorphin is positively correlated with the palatability of taste stimuli, and that CSF β-endorphin also reflects the reinforcement of fluid intake in thirsty animals.

Glutamate and the Flavor of Foods

Investigations of the effects of glutamic acid or its salts on the flavor, hedonic characteristics or acceptance of foods have emphasized a sodium salt of L-glutamic acid, monosodium glutamate (MSG). Food palatability increased with appropriate concentrations of MSG, and could be represented f(MSG and NaCl) as points on the surface of an elliptic paraboloid. Hedonic effects differed between foods, were a function of concentrations of MSG and other ingredients and did not necessarily become positive when only MSG was added. For example, with boiled or fried rice, ratings were neutral or negative with MSG alone, positive for fried rice with MSG and NaCl, but positive for boiled rice only if soy sauce was also added. A one-dish meal, Chinese noodle, became positive with an appropriate concentration of NaCl plus a MSG-5'ribonucleotide mixture, but not with NaCl alone. Flavor of meat, fish or vegetable stocks containing natural glutamates differed from that of quinine, sucrose, NaCl or acid solutions. Glutamates and free amino acids plus nucleotides were necessary for full boiled potato flavor. Overall, the effects of MSG on foods were different from those of NaCl but often interacted with NaCl, and positive effects were facilitated by low concentrations of 5'-ribonucleotides.

Relative taste thresholds for ethanol, saccharin, and quinine solutions in three strains of rats nonselected for ethanol: A comparative study.

Relative taste thresholds for ethanol, saccharin, and quinine solutions in three strains of rats nonselected for ethanol: A comparative study.

Stability, compatibility and plasticizer extraction of quinine injection added to infusion solutions and stored in polyvinyl chloride (PVC) containers

The stability of quinine was determined in various diluents and in polyvinyl chloride (PVC) containers. The release of diethyhexyl phthalate (DEHP) from PVC bags into intravenous infusions of quinine was also measured. We used an injection of two doses of quinine; quiniforme at 500 mg and quinimax at 400 mg in either 250- or 500-ml PVC infusion bags containing 5% dextrose, to give initial nominal concentrations of 2 or 1 mg ml −1 quiniforme and 1.6 or 0.8 mg ml −1 quinimax, the mean concentrations commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of quinine would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of quiniforme and quinimax over 1- or 2-h simulated infusion irrespective of the diluent, and storage during 8 h at 22°C, 48 or 72 h at 4°C and 96 h at 45°C. Leaching of DEHP was also detected during simulated infusion delivery using PVC bags and PVC administration sets. The quantity was less than 2 μg ml −1. During storage at 4°C and room temperature the leaching of DEHP was low, but when the temperature was 45°C the quantity was high, 21 μg ml −1. To minimise patient exposure to DEHP, quinine solutions with all drugs should be infused immediately or stored for a maximum of 48 h at 4°C.

Neuroanatomy of the panic-respiration system

Drinking behavior is regulated by endogenous factors such as the hydration condition of animals and exogenous factors such as the taste of ingested fluids. These factors have been suggested to interact with each other via serotonergic (5-HT) signaling to regulate drinking behavior. In the present study, we examined how dehydration affects the intake of bitter water, which suppresses drinking behavior, via 5-HT signaling. Water deprivation increased water intake for 1 h, depending on the duration of water deprivation. The intake of 1 mM quinine, which is a bitter tastant, was lower than that of water in mice deprived of water for 24 h but not 48 h. We next examined the involvement of the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN), which contain a large population of 5-HT neurons, in changing tolerance for quinine intake after water deprivation. The intake of quinine following water deprivation for 24 h, but not 48 h, increased the number of tryptophan hydroxylase-positive neurons expressing c-Fos in the DRN, but not in the MRN. Moreover, administration of paroxetine, a selective serotonin reuptake inhibitor, decreased the intake of quinine solution, but not water, in mice deprived of water for 48 h, indicating that paroxetine treatment restored the aversion to quinine. These results suggest that unresponsiveness of 5-HT neurons in the DRN may be involved in the dehydration-induced increase in tolerance for bitter water.

Quantitative trait loci associated with short-term intake of sucrose, saccharin and quinine solutions in laboratory mice.

The goal of this study was simultaneously to map two genetic loci which, collectively, have a large effect on intake of sucrose, saccharin and quinine solutions in mice. These loci had been previously identified using long-term measurements with the traditional two-bottle test, but the present study used a short-term, one-bottle test. Intake of distilled water, 100 mM sucrose, 10 mM sodium saccharin and 1.1 mM quinine HCl over 6 h was measured on two occasions from a non-deprived group of 61 male and 72 female F2 mice derived from a cross of the C57BL/6J and DBA/2J mouse strains and used to detect quantitative trait loci (QTL). DNA from each animal was typed for polymorphisms in anonymous microsatellite markers on mouse chromosomes 4 and 6. Saccharin and sucrose relevant QTL were detected on distal chromosome 4 and a quinine relevant QTL was detected on medial/distal chromosome 6 in the region of Prp. The location of these QTL and the proportion of phenotypic variance they accounted for were similar to those arrived at following previous determinations using the two-bottle test. Measurement stability for the three gustatory phenotypes was high, product-moment correlation coefficients between first and second determinations varying between approximately 0.80 for sucrose and saccharin and 0.73 for quinine. QTL parameters assessed independently for first and second presentations of sucrose and saccharin were stable, but the location of the quinine QTL differed between presentations. The present experiment illustrates the utility of a 6 h fluid intake test in the mapping of Sac and Qui loci. The short duration of the test provides a simple means of measuring variation in gustatory processes and the discovery that these loci influence short-term as well as long-term fluid intake extends understanding of the mechanism of gene action.

Hyperresponsiveness to Palatable and Aversive Taste Stimuli in Genetically Obese (Bombesin Receptor Subtype-3–Deficient) Mice

Taste preference in obese mice was examined using genetically obese (bombesin receptor subtype-3: BRS-3–deficient) animals. Preference for either sodium saccharin (0.2%), sodium chloride (0.9%), citric acid (0.1%), or quinine sulfate (0.002%) solution was examined using a two-bottle test situation, and BRS-3–deficient mice not only showed a stronger preference for saccharin solution, but also a stronger aversive response to quinine solution, relative to wild-type littermates. Furthermore, a conditioned taste-aversion test measured the consumption of sodium saccharin (0.2%) and sodium chloride (0.9%) solutions after intraperitoneal injection of LiCl (0.3 M, 1 mg/kg), and BRS-3–deficient mice exhibited stronger aversion to both solutions than did control animals. In situ hybridization demonstrated that the BRS-3 gene is expressed in the parabrachial nucleus, the medial and central nuclei of the amygdala, and the hypothalamic nuclei such as paraventricular nucleus, all of which are known to be involved in taste perception. These results suggest that expression of the BRS-3 gene in these nuclei is important for the modulation of taste preference, as well as the development of obesity.

Taste Reactivity in Alcohol-Preferring AA and Alcohol-Avoiding ANA Rats

BADIA-ELDER, N. E. AND S. W. KIEFER. Taste reactivity in alcohol-preferring AA and alcohol-avoiding ANA rats. ALCOHOL 18(2/3) 159–163, 1999.—Alcohol-preferring rats (Alko alcohol or AA) were tested for taste reactivity to water, sucrose, quinine, and a range of alcohol concentrations (5–40%) both before and after a period of continuous alcohol access. The alcohol-avoiding line of rats (Alko nonalcohol or ANA) was also tested for comparison. It was found that AA rats displayed greater ingestive reactivity to alcohol compared to ANA rats both before and after a three-week period of continuous access to 10% alcohol (during which time AA rats drank significantly more alcohol than ANA rats). AA rats also made significantly more ingestive responses to a 0.3 M sucrose solution and a 0.0005 M quinine solution. Differences between AA rats and ANA rats in aversive reactivity appeared only after the alcohol consumption tests; AA rats made significantly fewer aversive responses to the 30% and 40% concentrations after continuous alcohol access. AA rats also made significantly more aversive responses to the quinine solution. The results suggest that line differences between AA rats and ANA rats in the reactivity response to alcohol solutions have been selected in association with the original selection phenotype of alcohol consumption.

Isosmotic modulation of Ca2+-regulated exocytosis in guinea-pig antral mucous cells: role of cell volume.

1. Exocytotic events and changes of cell volume in mucous cells from guinea-pig antrum were examined by video-enhanced optical microscopy. 2. Acetylcholine (ACh) evoked exocytotic events following cell shrinkage, the frequency and extent of which depended on the ACh concentration. ACh actions were mimicked by ionomycin and thapsigargin, and inhibited by Ca2+-free solution and Ca2+ channel blockers (Ni2+, Cd2+ and nifedipine). Application of 100 microM W-7, a calmodulin inhibitor, also inhibited the ACh-induced exocytotic events. These results indicate that ACh actions are mediated by intracellular Ca2+ concentration ([Ca2+]i) in antral mucous cells. 3. The effects of ion channel blockers on exocytotic events and cell shrinkage evoked by ACh were examined. Inhibition of KCl release (quinine, Ba2+, NPPB or KCl solution) suppressed both the exocytotic events and cell shrinkage evoked by ACh. 4. Bumetanide (inhibition of NaCl entry) or Cl--free solution (increasing Cl- release and inhibition of NaCl entry) evoked exocytotic events following cell shrinkage in unstimulated antral mucous cells and caused further cell shrinkage and increases in the frequency of exocytotic events in ACh-stimulated cells. However, Cl--free solution did not evoke exocytotic events in unstimulated cells in the absence of extracellular Ca2+, although cell shrinkage occurred. 5. To examine the effects of cell volume on ACh-evoked exocytosis, the cell volume was altered by increasing the extracellular K+ concentration. The results showed that cell shrinkage increases the frequency of ACh-evoked exocytotic events and cell swelling decreases them. 6. Osmotic shrinkage or swelling caused the frequency of ACh-evoked exocytotic events to increase. This suggests that the effects of cell volume on ACh-evoked exocytosis under anisosmotic conditions may not be the same as those under isosmotic conditions. 7. In antral mucous cells, Ca2+-regulated exocytosis is modulated by cell shrinkage under isosmotic conditions.

Neuronal mechanisms of site-specific nociceptive sensitization in the common snail.

Comparative studies of the electrophysiological effects of site-specific nociceptive sensitization were performed on LPl1 and RPl1 command neurons in the common snail, after placing concentrated quinine solution (10%) on the animal's head or mantle ridge. Greater synaptic facilitation was observed in command neuron responses to tactile test stimuli applied to the same part of the body as the sensitizing stimulus, as compared with the level of synaptic facilitation in responses to tactile stimulation of other parts of the body. Synaptic facilitation of responses of neurons LPl1 and RPl1 to tactile stimulation of the head appeared 1 h after sensitizing stimulation and consisted of two phases: the first phase was characterized by a peak-like increase in the area of slow EPSP (sEPSP) and lasted 1 h; the second phase was characterized by maintenance of a relatively stable level of facilitation of sEPSP, which lasted to the end of the observation period (2-3 h). Synaptic facilitation of neuron responses to tactile stimulation of the mantle ridge appeared 40-60 min after facilitation of responses to test stimulation of the snail's head, and was characterized by maintenance of a relatively stable level of sEPSP facilitation. It is suggested that the specificity of synaptic facilitation occurring in snail defensive behavior command neurons during the period of long-term nociceptive sensitization is associated with the genetic regulation of the various synaptic "inputs" to neurons.

Establishing oral preference for quinine, phencyclidine and caffeine solutions in rats.

Rats were given fixed-time, 1-min food-pellet delivery sessions, for 3 h every day, which resulted in over drinking (schedule-induced polydipsia). In previous research, groups of animals came to prefer solutions of cocaine or lidocaine to concurrently presented water, if the drugs were first offered in a glucose/saccharin vehicle, which was then gradually eliminated, so that the choice became a drug solution in water vehicle versus water. In the present experiment, the same procedure produced a preference for 0.025 mg/ml quinine solution to water, indicating that a bitter solution that was not a topical anesthetic agent could come to be preferred. After establishing preference for quinine solution, it was possible to gradually remove quinine while increasing phencyclidine (PCP) concentration to produce preference for 0.075 mg/ml PCP solution, and similarly to produce subsequent preference for 0.1 mg/ml caffeine solution, although not for all animals. For additional groups, drinking either 0.15 mg/ml PCP or 0.1 mg/ml caffeine, while gradually reducing the glucose/saccharin vehicle to water vehicle was a less successful procedure for establishing the respective drug preferences. The latter result suggests that first instituting a preference for quinine solution to water facilitated the later establishment of preferences for PCP and caffeine solutions.

Training and characterization of a quinine taste discrimination in rhesus monkeys.

There is a limited amount of information available about taste as a discriminative stimulus in non-human primates. The objective of this study was to establish a bitter taste (quinine sulfate) as a cue for lever selection and food reward in rhesus monkeys. Training took place in a series of steps that culminated in a schedule in which five lip contacts on a spout produced either quinine solution or water, followed by an opportunity to earn a food pellet by completing 20 presses on one of two levers. Responses on one of the levers resulted in food delivery if the solution contained quinine; responses on the other lever resulted in food delivery if the solution was water. A single session consisted of 100 randomly ordered taste trials with a 60-s interval between each trial. All of the animals acquired the discrimination, and the lowest quinine concentration that maintained consistent behavior was 0.3 mg/ml. To assess the specificity of the discrimination, compounds from other human taste categories were tested. A series of compounds that are detected as "bitter" by humans (caffeine, 1.5x10(-3) M; strychnine, 9x10(-4) M; PTC, 6x10(-5) M, denatonium benzoate, 2.24x10(-4) M; and urea, 3.0x10(-1) M) produced full generalization to the quinine sulfate discriminative stimulus, while "sweet" (sucrose, 2.9x10(-2) M) and "salty" (sodium chloride, 1.4 M) stimuli did not. There was individual variation among animals in response to "sour" compounds; acetic acid did not generalize to quinine, but HCl acid produced full generalization in one of three animals. These results suggest that a "bitter" taste cue is controlling the quinine discrimination.

Selective breeding for high and low alcohol preference in mice.

High and low alcohol preference (HAP and LAP, respectively) mice were created by 10 generations of bidirectional selection for differences in two-bottle choice alcohol consumption. The progenitors used for selection were HS/lbg mice, which are a genetically defined, outbred stock. During selection, mice had 24-h, daily access to 10% alcohol (v/v) and water ad libitum for 30 days and were selected based on the alcohol (g/kg) consumed per day over the entire period. Food was available ad libitum. At S10, line means for alcohol consumption differed greatly, with consumption of over 12 g/kg per day in the HAP mice and less than 2 g/kg per day in the LAP mice. Realized heritability for bidirectional selection was approximately 0.2. Female mice consumed more alcohol than male mice. There were no differences between lines in alcohol elimination rate, nor were there line differences in intake of salt or quinine solutions. However, consumption of saccharin solutions was greater in HAP mice than LAP mice, consistent with previous findings of a genetic correlation between sweet preference and alcohol drinking. Because the mouse genome is relatively well characterized, these selected lines should prove a useful tool for assessment of the genetic basis of, and phenotypes that correlate with, alcohol drinking.

Exposure to Sucrose–Quinine Solutions Does Not Increase Ethanol Consumption

The taste of ethanol can be aversive or preferred based on prior experience with ethanol consumption. A preference for ethanol’s taste is thought to result from the association of ethanol’s taste with its neuropharmacological activity. However, acclimation to ethanol’s aversive taste may also play a role in increased ethanol consumption following prolonged exposure. The present study examined if acclimation to a bitter–sweet tastant, which has been suggested to share similar taste qualities with ethanol, would increase ethanol intake with only minimal prior experience of an association of ethanol intake with its neuropharmacological activity. Male Long–Evans rats were trained to drink 10% sucrose during 20-min sessions. The consumption of 0–20% ethanol was then determined before and after exposure to a sucrose–quinine solution. Before the sucrose–quinine taste acclimation procedure, the initial intake of sucrose–quinine was low and similar to 5% ethanol. After the acclimation procedure, increases in sucrose–quinine intake, but not ethanol intake, were observed. These data could indicate that any similarity in the taste qualities of sucrose–quinine and ethanol solutions are diminished following exposure to sucrose–quinine. Alternatively, the differential changes in sucrose–quinine and ethanol intake could be the result of being differentially regulated by a combination of taste and postingestive factors. Overall, these data indicate that exposure to sucrose-quinine, which resulted in increased intake of sucrose–quinine, was not sufficient to alter ethanol intake. Rather, exposure to taste and postingestive factors associated with ethanol may be necessary to increase ethanol intake.

6- n-Propylthiouracil: A Genetic Marker for Taste, with Implications for Food Preference and Dietary Habits

6-n-Propylthiouracil (PROP) and phenythiocarbamide (PTC) are members of a class of compounds known as “thioureas.” These compounds carry the chemical group N-C=S, which is responsible for their characteristic bitter taste (for review, see Bartoshuk et al. 1994; Drewnowski and Rock 1995). As is true for many scientific discoveries, the bitterness of PROP and PTC were discovered by accident. In 1931, while Fox was synthesizing PTC in his laboratory, some of the white crystals became airborne. His colleagues perceived a bitter taste, but Fox tasted nothing.

The Effects of Restraint Stress on Intake of Preferred and Nonpreferred Solutions in Rodents

In these experiments we determined whether stress influenced intake of different flavored test solutions or only those that were preferred. In a series of studies, rats or hamsters were exposed to acute (1 h) or repeated (3 h/day for 3 days) restraint stress immediately followed by access to one of four tastants (saccharin, salt, citric acid, or quinine solutions) paired with water in a 24-h preference test. As rats prefer salt and hamsters do not, both species were used to test the effects of stress on preferred vs. nonpreferred solutions using the same stimulus. Acute restraint inhibited intake of saccharin in rats but had no effect on preference, indicating that suppression of intake was not due to changes in hedonic response. Restraint had no effect on saccharin intake of hamsters but significantly increased salt intake. However, as the preference ratio remained low for the solution (0.26), the stress-induced increase in salt intake was probably associated with a disturbance of sodium and fluid balance rather than a change in sensory perception. This was supported by stress having no effect on intake of nonpreferred solutions in rats or hamsters. Repeated restraint had no effect on salt or saccharin intake of rats when test solutions were presented after stress, but rats showed no preference for saccharin in a subsequent study in which the solution was associated with onset of stress. These results indicate that stress has specific effects on saccharin and salt intake that are not limited to preferred solutions.

Serotonin imitates several of the neuronal effects of nociceptive sensitization in the common snail.

Experiments on defensive behavior command neurons in common snails showed that synaptic facilitation in the responses of nerve cells to sensory stimulation occurs 50-60 min after the onset of application of serotonin (10 microM) to the CNS. The properties of neuron electrogenic membranes (membrane potential, membrane excitability) did not change after exposure to serotonin. Along with synaptic facilitation, serotonin (100 microM) increased the excitability and produced minimal depolarization of the membranes of command neurons. Serotonin had selective effects on the reactions of neurons to different sensory stimuli: facilitation of neuron responses to tactile stimulation of the head lasted 1 h, while responses to application of dilute quinine solution lasted 2-3 h; serotonin facilitated neuron responses to tactile stimulation only of the snail's head, and did not alter the responses to stimulation of the foot or the mantle ridge. The time course of the electrophysiological effects of serotonin coincided with changes in bound calcium (Cab) levels in command neurons. This set of serotonin-induced neurophysiological effects is similar to the effects resulting from the development of nociceptive sensitization. It is suggested that serotonin is involved in the mechanisms of transient changes and consolidation of long-term plastic rearrangements in command neurons which underlie sensitization.