Long term effects of quinine on food intake and body weight in the rat

Adulteration of a chow diet with 0.75% quinine sulfate produces a short-lived decrement in food intake in both ad lib-fed and previously food-restricted adult female rats. In contrast, quinine produces a long-lasting depression in body weight; ad lib access to quinine-treated chow results in a plateauing of body weight at a lower level until quinine is removed from the diet, despite recovery of food intake.     

Taste perception of bitter compounds in young and elderly persons: Relation to lipophilicity of bitter compounds

Threshold and suprathreshold sensitivities to 13 bitter compounds were determined for 16 young adults (mean age = 27.4 years) and 18 elderly persons (mean age = 81.3 years). Half of the subjects in each age group were tasters of the bitter compound phenylthiocarbamide (PTC) and half were nontasters. Both detection and recognition thresholds, determined by a forced-choice ascending detection method, were elevated in older subjects; there were no significant differences in threshold values between tasters and nontasters of PTC. A strong relationship between bitter threshold values and the logarithm of the octanol/water partition coefficient was found for both young and elderly subjects. For young subjects, suprathreshold bitterness ratings were more intense for tasters of PTC compared with nontasters. Significant losses in suprathreshold sensitivity to bitter tastants with age were also found. However, unlike threshold sensitivity, no relationship was found between suprathreshold bitter taste intensity and lipophilicity.     

Bitter taste and blood glucose are not involved in the suppressive effect of dietary histidine on food intake

Histamine decreases food intake by activating histaminergic neurons in the hypothalamus. Histamine is synthesized by histidine decarboxylase (HDC) from histidine. The purpose of this three-part animal study was to clarify the mechanism underlying the suppressive effect of dietary histidine on food intake. In experiment 1, we attempted to distinguish palatability from a direct effect of dietary histidine because histidine tastes slightly bitter to humans. We measured food intake every hour for 24 h in rats fed with a histidine-enriched diet or one of various quinine diets (0.001–0.8% quinine), also bitter. In experiment 2, we measured changes in blood glucose levels in rats fed with a standard or histidine-enriched diet because blood glucose is known to decrease food intake. In experiment 3, we intraperitoneally injected fluoromethylhistidine (FMH), an antagonistic inhibitor of HDC, in rats fed with a histidine-enriched diet. In experiment 1, food intake was almost the same in rats fed with the histidine-enriched diet as that in rats fed with the 0.01% quinine diet until 6 h, but food intake was low in other groups compared with that in the histidine-enriched diet group. After 6 h, food intake did not increase in rats fed with the histidine-enriched diet. In experiment 2, the blood glucose level rose quickly and then began to decrease at approximately 2 h in both groups of rats. However, it decreased more dramatically in rats fed with the histamine-enriched diet and reaches a significant difference from the decrease in the standard-diet group by 6 h. In experiment 3, food intake increased significantly in FMH-injected rats fed with the histidine-enriched diet compared with in non-FMH injected rats. Our results suggest that dietary histidine suppresses food intake by activating histaminergic neurons in the hypothalamus, independently bitter taste and blood glucose level.     

Differential effects of quinine and sucrose octa acetate on food intake in the rat

Twenty-seven adult female rats were fed chow diets containing quinine sulfate, sucrose octa acetate, or alphacel. Quinine produced a greater, more prolonged depression of food intake than did SOA. Quinine also resulted in loss of body weight.     

Dietary preference behavior in rats fed bitter tasting quinine and sucrose octa acetate adulterated diets

Rats were fed a bitter and presumably toxic quinine adulterated diet and a more bitter, but non-toxic sucrose octa acetate (SOA) adulterated diet. In two-diet preference tests the animals initially preferred the quinine diet over the SOA diet. After being fed only the SOA diet for four days the rats switched their preference to this diet during a subsequent two-diet preference test. In 10 day single diet tests the rats ate significantly more of the SOA diet than of the quinine diet. The results are consistent with the hypothesis that the toxic effects of quinine result in the formation of a conditioned taste aversion to the diet, and indicate that rats can distinguish between two bitter diets and develop a preference for the more bitter, but non-toxic one.     

Newborn rats' first suckling experience: taste differentiation and suckling plasticity

The present study examined responsiveness of newborn rats to a surrogate nipple providing fluids with basic tastes (sweet, sour, bitter and salty) and assessed the effects of this first gustatory experience on subsequent responding to the nipple itself (empty nipple) or the nipple providing water. Responsiveness (attachment to and ingestion from a surrogate nipple providing saccharin, saline, quinine or ammonium chloride) was compared with that toward a nipple providing water. Compared to water, saline and quinine significantly reduced attachment to and ingestion from the nipple, while saccharin and milk significantly increased attachment behavior. Ammonium chloride increased attachment but not ingestive behavior. Suckling experience with saline, quinine and ammonium chloride attenuated both attachment and ingestive behaviors when subjects were tested 1 h later with an empty surrogate nipple or a nipple providing water. Experience with saccharin and milk (but not water) increased both measures. The data suggest that in newborn rats, as early as a few hours after birth, mechanisms of gustatory detection have control over suckling behavior. Initial experience with the tastants available from the nipple in the first suckling episode may alter further responsiveness to the nipple itself, mediated perhaps by mechanisms of appetitive and aversive conditioning.     

Post-ingestive effects of quinine on intake of nutritive and non-nutritive substances

Intragastric intubation of 0.75 g QHCl had no effect on 4 hr food intake, but produced anorexia over a 24 hr period when paired with consumption of a novel sucrose octa acetate (SOA) treated chow. No anorexia developed when a familiar food was available. SOA adulteration alone produced a decrement in food intake that persisted for 4 hr; this effect was independent of quinine intubation. In a second experiment, intubation of 0.375 or 0.75 g QHCl, 0.3 M LiCl, or 0.6 g SOA did not alter 4 hr chow intake, but QHCl and LiCl both produced pica that lasted for 4 hr. SOA and 0.75 g QHCl produced a 24 hr hyperphagia, while LiCl and 0.375 g QHCl produced no change in 24 hr chow intake.     

Bitter taste markers explain variability in vegetable sweetness, bitterness, and intake

Intake of vegetables falls short of recommendations to lower risk of chronic diseases. Most research addresses bitterness as a sensory deterrent to consuming vegetables. We examined bitter and sweet sensations from vegetables as mediators of vegetable preference and intake as well as how these tastes vary with markers of genetic variation in taste (3.2 mM 6-n-propylthiouracil bitterness) and taste pathology (1.0 mM quinine bitterness, chorda tympani nerve relative to whole mouth). Seventy-one females and 39 males (18-60 years) reported prototypical tastes from and preference for Brussels sprouts, kale and asparagus as well as servings of vegetables consumed, excluding salad and potatoes. Intensity and hedonic ratings were made with the general Labeled Magnitude Scale. Data were analyzed with multiple linear regression and structural equation modeling. Vegetable sweetness and bitterness were independent predictors of more or less preference for sampled vegetables and vegetable intake, respectively. Those who taste PROP as most bitter also tasted the vegetables as most bitter and least sweet. The spatial pattern of quinine bitterness, suggestive of insult to chorda tympani taste fibers, was associated with less bitterness and sweetness from vegetables. Via structural equation modeling, PROP best explained variability in vegetable preference and intake via vegetable bitterness whereas the quinine marker explained variability in vegetable preference and intake via vegetable bitterness and sweetness. In summary, bitterness and sweetness of sampled vegetables varied by taste genetic and taste function markers, which explained differences in preference for vegetables tasted in the laboratory as well as overall vegetable intake outside the laboratory.     

Oral sensory phenotype identifies level of sugar and fat required for maximal liking

A half-century ago, Fischer and colleagues found correlations between food preference and genetic markers of taste [6-n-propylthiouracil (PROP), quinine]. Recently, a number of studies report differences in sweet liking/disliking with taste phenotype or genotype. Here we modeled optimal liking for milk/sugar mixtures using the response surface method among 79 mostly normal weight adults (36 women) who reported low dietary restraint. Two non-overlapping phenotype analyses were performed: a) discordance in PROP versus quinine bitterness and b) number of fungiform papillae (FP, taste papillae on the tongue tip). Although all phenotype groups liked highly sweet and creamy sensations (in liking by sensation models), the fat and sugar levels for hedonic optima varied (in liking by concentration models). Males generally liked higher fat (20 to 40%) and sugar levels, with females disliking unsweetened cream. In quinine/PROP groups, liking peaked at 30% fat/15% sucrose for men and women who tasted 0.32 mM quinine more bitter than 3.2 mM PROP (n=15); a group previously shown to have highest sugar intakes (Duffy et al., 2003). Those tasting PROP more bitter than quinine (n=14) reported greater creamy/sweet sensations, with peak liking at lower fat and sweet levels (3.3% fat/10% sucrose). Generally, those in the high FP group perceived more creamy/sweet sensations with level of liking more influenced by sugar level, especially among high FP females. At high sugar/high fat levels low FP males and females retained this liking while liking fell off for those in the high FP group. In summary, although most liked sweet/creamy sensations, perceptual differences in these sensations varied with oral phenotype, explaining some of the differences in the amount of sugar and fat required to reach hedonic optima. A high affinity for high sugar/high fat mixtures among oral phenotype subgroups has relevance for energy consumption and could explain the link previously observed between oral sensation and body weight.     

Cycloheximide-induced inhibition of protein synthesis in hippocampal pyramidal neurons is time-dependent: Differences between CA1 and CA3 areas

Cycloheximide (CHI), an inhibitor of protein synthesis, is widely used for studying the mechanisms of consolidation of long-term memory (LTM). High concentrations of CHI inhibit the protein synthesis in brain homogenates by more than 80% and impair LTM consolidation. For understanding the mechanisms of consolidation, it is important to know how protein synthesis inhibitors affect hippocampal neurons. However, the effect of CHI on protein synthesis in CA1 and CA3 hippocampal pyramidal neurons is still poorly understood. In the present work, the state of ribosomes in CA1 and CA3 pyramidal neurons from the dorsal hippocampus of Wistar rats 1, 2, 4, and 72 h after the introcerebroventricular (i.c.v.) injection of a high concentration of CHI was determined using the fluorescent dye acridine orange. We showed that CHI induces great differences in the dynamics of the intensity of protein synthesis in CA1 and CA3 pyramidal neurons. The suppression of the intensity of protein synthesis in CA1 pyramidal neurons 1 h after the injection of CHI was more than threefold stronger than in CA3, and by 4 h, it was most pronounced in CA3 neurons. We suggest that the protein synthesis in CA1 pyramidal neurons contributes significantly to the synaptic consolidation of declarative memory in the first critical period.     

Facial and affective reactions to tastes and their modulation by sadness and joy

This study examined adults' affective and facial reactions to tastes which differ in quality and valence, and the impact of sadness and joy on these reactions. Thirty-six male and female subjects participated voluntarily. Subjects each tasted 6 ml of a sweet chocolate drink, a bitter quinine solution (0.0015 M) and a bitter-sweet soft drink. Following a baseline period, either joy or sadness was induced using film clips before the same taste stimuli were presented for a second time. Subjects rated the drinks' pleasantness and intensity of taste immediately after each stimulus presentation. Facial reactions were videotaped and analysed using the Facial Action Coding System (FACS [P. Ekman, W.V. Friesen, Facial Action Coding System: Manual. Palo Alto, CA: Consulting Psychologists Press; 1978., P. Ekman, W. Friesen, J. Hager, Facial Action Coding System. Salt Lake City, Utah: Research Nexus; 2002.]). The results strongly indicated that the tastes produced specific facial reactions that bear strong similarities to the facial reactivity patterns found in human newborns. The data also suggest that some adults' facial reactions serve additional communicative functions. Emotions modulated taste ratings, but not facial reactions to tastes. In particular, ratings of the sweet stimulus were modulated in congruence with emotion quality, such that joy increased and sadness decreased the pleasantness and sweetness of the sweet stimulus. No emotion-congruent modulation was found for the pleasantness and intensity ratings of the bitter or the bitter-sweet stimulus. This 'robustness' of bitter taste ratings may reflect a biologically meaningful mechanism.     

Taste responses in wild and domestic guinea pigs

Responses of male wild (Cavia aperea) and domestic (C. Porcellus) guinea pigs to stimuli representing the taste qualities sweet, salty, sour and bitter were monitored in two bottle choice tests. Wild cavies showed statistically significant preferences for .008–.25 M NaCl and .001–.031 M sodium saccharin and rejected 1.0 M NaCl and .063 M citric acid. Domestic cavies' acceptances of solutions preferred by the wild form were lower on first series of presentations but increased to the level of C. aperea upon representations. C. porcellus rejected citric acid (.031 M), NaCl (.5 M) and sucrose octaacetate (.001 M) at concentrations not rejected by the wild type. Wild cavies did not reject SOA at any concentration and neither type rejected quinine sulfate. Absence of bitter rejection was postulated to be an adapatation useful to some herbivores. Changes in acceptance data over time and the interference of position preference with responses to solutions suggested the major difference between types to be the wild cavies' greater readiness to orient to stimulus cues.     

Saccharin stimulates the "deterrent" cell in the blowfly: behavioral and electrophysiological evidence

In the attempt to gain more information on the mechanisms underlying bitter and/or sweet taste reception, we have investigated the responses of labellar chemosensilla in the blowfly Protophormia terraenovae to Na-saccharin, as compared to sweet stimuli (sucrose or fructose) and bitter stimuli (denatonium benzoate or amiloride). Electrophysiological and behavioral results indicate that the sweetener Na-saccharin inhibits the “sugar” cell in the labellar taste sensilla of the blowfly P. terraenovae. In multichoice preference tests, flies ingested more of the solutions containing sugar to those with sugar+Na-saccharin. This finding is in good agreement with the spike frequency reduction observed for the “sugar” cell activity. Analysis of the spike discharges also shows a positive dose–response for the “deterrent” cell following stimulation with Na-saccharin and denatonium benzoate. Flies drank any of the Na-saccharin solutions, regardless of their concentration, less than water, thus indicating a weak deterring effect on water drinking. The prevailing activation of the “deterrent” cell by stimulation with Na-saccharin is not directly coupled with a coherent behavioral output. Cross adaptation was found to occur between responses to Na-saccharin and denatonium benzoate or amiloride regardless of the order of adapting stimuli. In the case of sweet stimuli, cross adaptation occurred when the adapting stimulus was Na-saccharin, but it did not when the adapting stimuli were sucrose or fructose. Addition of Na-saccharin to both sugars significantly depressed the spike firing frequency, while an increase was observed with denatonium benzoate or amiloride.     

Sweet and bitter tastes of alcoholic beverages mediate alcohol intake in of-age undergraduates

Alcoholic beverages are complex stimuli, giving rise to sensations that promote or inhibit intake. Previous research has shown associations between 6-n-propylthiouracil (PROP) bitterness, one marker of genetic variation in taste, and alcohol behaviors. We tested the PROP bitterness and alcohol intake relationship as mediated by tastes of sampled alcoholic beverages. Forty-nine undergraduates (mean age=22 years) participated. According to the Alcohol Use Disorders Identification Test (AUDIT), only 3 of 49 subjects reported patterns indicating problematic drinking. Participants used the general Labeled Magnitude Scale to rate PROP bitterness and tastes from and preference for Pilsner beer, blended scotch whiskey, instant espresso and unsweetened grapefruit juice. Alcohol intake was reported over a typical week. Regression analysis tested the hypothesis that PROP bitterness influenced alcohol bitterness and sweetness, which in turn predicted alcohol intake. Those who tasted less PROP bitterness tasted all beverages as less bitter and more preferred. Sweetness of scotch was significantly greater in those who tasted PROP as least bitter. For scotch, greater sweetness and less bitterness from sampled scotch were direct predictors of greater alcohol intake. For beer, preference ratings were better predictors of alcohol intake than the bitter or sweet tastes of the sampled beer. These findings support that PROP bitterness predicts both positive and negative tastes from alcoholic beverages and that those tastes may predict alcohol intake. The college environment may attenuate direct effects of PROP bitterness and intake. Here, PROP bitterness does not predict alcohol intake directly, but acts instead through sweet and bitter tastes of alcoholic beverages.     

Early experience with sour and bitter solutions increases subsequent ingestion.

Rats exposed to quinine or citric acid solutions during nursing, during the early postweaning period, or during both nursing and early postweaning showed a modification in their voluntary ingestion of these substances. With quinine, the most effective period of exposure was after weaning. Rats exposed to quinine during the post weaning period or in adulthood showed increased quinine ingestion. Rats exposed to quinine during nursing, however, did not show increased quinine ingestion even if additional exposure to quinine was given postweaning. In contrast, rats exposed to citric acid while nursing showed an increased voluntary ingestion of citric acid compared to animals exposed to citric acid either after weaning or not exposed to citric acid at all. Both sour and bitter tastes are commonly thought to be innately aversive substances; however, with appropriate developmental experience, an animal's response to bitter and sour substances can be modified. The alteration of expected taste preferences or aversions through experience may be seen as one mechanism accounting for certain human food preferences.     

Age and sex effects on taste of sucrose, NaCl, citric acid and caffeine

A procedure combining forced choice discrimination with intensity scaling served to evaluate taste perception of sucrose, NaCl, citric acid and caffeine in 24 young and 24 geriatric subjects. Each group was divided equally by sex. No overall sex differences occurred for taste discrimination, and suprathreshold taste intensity scaling for sucrose and NaCl did not differ by sex or age. However, young adults generally discriminated lower concentrations of citric acid and caffeine from water blanks than did geriatric subjects. Younger subjects judged suprathreshold concentrations of caffeine significantly more intense, as did young females compared to young males; similarly, young females judged citric acid as stronger than did older males. The present results suggest that age and gender are major factors in sour and bitter perception.     

Age and sex effects on taste of sucrose, NaCl, citric acid and caffeine

A procedure combining forced choice discrimination with intensity scaling served to evaluate taste perception of sucrose, NaCl, citric acid and caffeine in 24 young and 24 geriatric subjects. Each group was divided equally by sex. No overall sex differences occurred for taste discrimination, and suprathreshold taste intensity scaling for sucrose and NaCl did not differ by sex or age. However, young adults generally discriminated lower concentrations of citric acid and caffeine from water blanks than did geriatric subjects. Younger subjects judged suprathreshold concentrations of caffeine significantly more intense, as did young females compared to young males; similarly, young females judged citric acid as stronger than did older males. The present results suggest that age and gender are major factors in sour and bitter perception.     

Effects of quinidine and quinine on the excitability of pyramidal neurons in guinea-pig hippocampal slices

Effects of quinidine (25M–1mM) and its stereoisomer, quinine (1–5 mM), on the excitability of CA3 pyramidal neurons were investigated in guinea-pig hippocampal slices using intracellular recording techniques. At concentrations of quinidine higher than 100 M (and higher than 1 mM for quinine), 1) the resting potential shifted to the depolarizing direction with an increase of the input resistance, 2) the spike duration was prolonged, 3) the spike amplitude was decreased, 4) the late component of the afterhyperpolarization (AHP) (caused by the activity of the Ca²⁺-mediated K conductance) were suppressed, and 5) finally, neurons became inexcitable. The results indicate that the blocking action of quinidine and quinine is not specific to the Ca²⁺-mediated K conductance in mammalian hippocampal neurons, and that this conductance is much less sensitive to the drugs in comparison with other preparations.     

Palatability, food intake and the behavioural satiety sequence in male rats

Food intake is influenced not only by nutritional status but also by diverse environmental factors. Indeed, a unique quality of food reward is its strong modulation by palatability cues, such as taste, with animals generally preferring diets that are sweet and avoiding those that are either bitter or sour. As appetite suppressants (including those currently in development) could alter food intake by modifying taste sensitivity and/or palatability, the aim of the present study was to characterise the influence of taste adulteration on the normal structure of feeding behaviour, i.e., the behavioural satiety sequence (BSS). Adult male rats were initially habituated both to the basic test diet (mash) and the test arena. Following stabilisation of basal intake, a continuous monitoring technique was used to profile behaviour in weekly 1-h sessions during which the animals were presented, in counterbalanced order, with the basic diet (control) or one of four taste-adulterated variants (0.015% quinine, 0.04% quinine, 0.2% saccharin, 0.3% saccharin). Food intake was strongly suppressed by the higher quinine concentration but was not significantly altered by any of the other additives. Behavioural analysis revealed that this anorectic-like response to 0.04% quinine-adulterated food was associated with a significant reduction in the peak feeding response, highly atypical intermittent food sampling/digging and the virtual absence of resting behaviour. Importantly, this pattern of behavioural change is readily distinguishable from those seen in response to other manipulations that reduce intake, including selective anorectics, sedatives and psychostimulants. Despite the lack of significant effect on food intake or the duration of feeding behaviour, dietary adulteration with 0.015% quinine (and, to a lesser degree, 0.3% saccharin) produced some effects on behavioural structure/time course consistent with a mild aversive response, i.e., bouts of midsession food sampling and a delay in the transition from eating to resting. Data are discussed in relation to the specific behavioural signature to quinine-induced anorexia and its potential utility in identifying appetite suppressants that may modify intake via changes in taste sensitivity and/or palatability.     

Difference in receptive field features of taste neurons in rat granular and dysgranular insular cortices

Summary Receptive fields (RFs) of 59 cortical taste neurons (35 in the granular insular area, area GI, 21 in the dysgranular insular area, area DI, and 3 in the agranular insular area, area AI) were identified in the oral cavity of the rat. The fraction of the neurons with RFs in the anterior oral cavity only was significantly larger in area GI (74.3%) than in area DI (42.9%). On the other hand, the fraction of neurons with RFs in both the anterior and posterior oral cavity was larger in area DI (42.9%) than in area GI (11.4%). On the whole, it is suggested that area GI is involved in discrimination of several taste stimuli in the oral cavity, whereas in area DI taste information originating from various regions of the oral cavity is integrated. When neurons were classified according to the best stimulus which most excited the neuron among the four basic tastes, different categories of taste neurons had RFs in different parts of the oral cavity. It is suggested that, in either taste area, different categories of taste neurons are involved in different sorts of taste coding. The majority of neurons in both areas had bilateral RFs. In area GI, neurons with RFs on single subpopulations of taste buds were significantly more numerous at the rostral region of the cortex than at the caudal region. There was no such relation between RF types and cortical localization in area DI. Otherwise, topographic representation of the oral cavity by taste neurons on the cortical surface was not obvious. RF features of taste neurons did not differ across layers in either cortical area.