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.     

Effects of quinine adulterated diets on the food intake and body weight of obese and non-obese hypothalamic hyperphagic rats

Female rats given knife cuts between the medial and lateral hypothalamus overate and became obese on a high fat diet. When switched to a quinine diet the knife cut rats initially underate and lost weight, but their body weights did not fall significantly below that of controls maintained on the same diet. Knife cut rats also maintained weights at control levels when given a moderately bitter quinine diet immediately after surgery, but displayed subnormal weights when switched to a very bitter diet. Cuts lateral to the fornix produced a greater weight suppression on the quinine diet, but a smaller weight gain on a high fat diet than did cuts medial to the fornix. The results indicate that the hypothalamic knife cuts elevate the upper limit of body weight with little or no change in the lower body weight limit, and that obesity rather than hypothalamic damage per se is the major cause of the hyperphagic rat's finickiness to unpalatable quinine diets. A dual lipostatic model of the hypothalamic hyperphagia syndrome is discussed.     

Experimental obesity syndromes in rats: influence of diet palatability on maintenace body weights

Female rats with ventromedial hypothalamic (VMH) lesions, parasagittal hypothalamic knife cuts (KC), or dorsolateral tegmental (DLT) lesions were maintained successively on 0.2 and 0.4% quinine chow, plain chow, pellets, wet mash, and high fat diets (15–45 days each). Only VMH rats overate the 0.2% quinine diet and only KC rats underate the 0.4% quinine diet. Although DLT rats did not overeat the unadulterated chow and pellet diets, as did VMH and KC rats, all three surgical groups attained roughly comparable elevated body weight means after access to the wet mash and high fat diets. Thus, dietary manipulations clearly induce differential patterns of feeding behavior in these three obesity syndromes.     

Dietary quinine reduces body weight and food intake independent of aversive taste

Separate groups of rats were chronically fed diets adulterated with either bitter tasting quinine sulfate (QSO₄), equal amounts of quinine in the less bitter form of quinine tannate (QT), or an amount of sucrose octaacetate (SOA) determined to have aversive taste properties equal to the QSO₄ diet. Dietary adulteration with SOA did not affect food intake or body weight. Dietary adulteration with quinine resulted in an initial reduction in food intake that showed a relative recovery but remained depressed compared to the intake of a group eating a quinine-free diet. Ingestion of diets containing equal amounts of quinine base resulted in equivalent chronic body weight reductions, despite different aversive diet characteristics. These results suggest that bitter taste is not the significant variable underlying the body weight effects of quinine but that quinine exerts some postingestive effect on body weight mediated by a slight but sustained decrease in the level of energy intake.     

Conditioned taste aversion in lean and obese rats with ventromedial hypothalamic knife cuts

The development of a conditioned taste aversion (CTA) was assessed in rats made hyperphagic with parasagittal knife cuts in the ventromedial hypothalamus (VMH). The animals were water deprived and presented with a .1% saccharin solution paired with injections of either lithium chloride or sodium chloride. In Experiment 1, VMH rats tested at a nonobese weight level did not differ from sham-operated control rats in the acquisition and extinction of the CTA. In Experiment 2, moderately obese VMH rats displayed a stronger CTA than did sham-operated control rats as evidenced by a slower rate of extinction. This effect was not due to the higher absolute dose of LiCl given to the obese VMH rats. A second group of obese VMH rats given an amount of LiCl equivalent to that given to the control rats also displayed retarded extinction of the CTA. The results of these experiments demonstrate that hyperphagia-inducing knife cuts do not alter aversive taste conditioning in rats but that hypothalamic obesity does enhance conditioned taste aversions. This may reflect an obesity-induced suppression in appetitive motivation.     

Ventromedial hypothalamic syndrome: Finickiness?

Female rats with lesions of the ventromedial hypothalamus (VMH) underate and lost weight compared to same-diet control rats when fed a 0.2% quinine-adulterated wet-mash maintenance diet, yet overate and gained weight compared to same-diet control rats when fed a 0.4% quinine-adulterated high-fat maintenance diet. Control rats underate and lost comparable amounts of body weight when fed either adulterated diet. These data question the generality of the concept of VMH finickiness and are discussed in terms of an increased hunger hypothesis.     

Sweet and Bitter Taste of Ethanol in C57BL/6J and DBA2/J Mouse Strains

Studies of inbred strains of rats and mice have suggested a positive association between strain variations in sweet taste and ethanol intake. However, strain associations by themselves are insufficient to support a functional link between taste and ethanol intake. We used conditioned taste aversion (CTA) to explore the sweet and bitter taste of ethanol and ability to detect sucrose, quinine and ethanol in C57BL/6J (B6) and DBA/2J (D2) mouse strains that are frequently used in alcohol research. The present study showed that C57BL/6J mice generalized taste aversions from sucrose and quinine solutions to 10% ethanol and, reciprocally, aversions to 10% ethanol generalized to each of these solutions presented separately. Only conditioned aversions to quinine generalized to ethanol in the DBA/2J strain but an aversion conditioned to ethanol did not generalize reciprocally to quinine. Thus, considering these two gustatory qualities, 10% ethanol tastes both sweet and bitter to B6 mice but only bitter to D2. Both strains were able to generalize taste aversions across different concentrations of the same compound. B6 were able to detect lower concentrations of quinine than D2 but both strains were able to detect sucrose and (in contrast to previous findings) ethanol at similar concentrations. The strain-dependent gustatory profiles for ethanol may make an important contribution to the understanding of the undoubtedly complex mechanisms influencing high ethanol preference of B6 and pronounced ethanol avoidance of D2 mice.     

The distinctiveness of ionic and nonionic bitter stimuli

The diverse chemical structures of stimuli that are bitter to humans suggest a need for multiple bitter receptors. Reactions of golden hamsters (Mesocricetus auratus) to 1 mM quinine hydrochloride, 3 mM denatonium benzoate, 180 mM magnesium sulfate, 30-100 mM caffeine, and 1-1.5 mM sucrose octaacetate (SOA) were studied to address whether there are multiple sensations elicited by bitter stimuli. Methods included behavioral generalization of LiCl-induced conditioned taste aversions (CTAs), intake preference tests, and electrophysiological recordings from the chorda tympani (CT) nerve. The five compounds, all bitter to humans, were all innately aversive to hamsters. CTA for the ionic quinine.HCl, denatonium benzoate, and MgSO(4) mutually cross-generalized and these ionic compounds were effective CT stimuli. Yet, the hamsters were much less sensitive to denatonium than humans, requiring a 100,000 times higher concentration for detection. CTA for nonionic caffeine and SOA did not cross-generalize to quinine or the other two ionic stimuli and these nonionic compounds were not effective CT stimuli. SOA and caffeine may elicit aversive reflexes or systemic reactions rather than taste sensations in the animals. Thus, the three ionic and two nonionic compounds form separate aversive stimulus classes in hamsters, neither of which appears to be a close homologue of the human bitter taste.     

A comparison of taste reactivity changes induced by ventromedial hypothalamic lesions and stria terminalis transections

A hyperreactivity to the sensory qualities of a food, i.e., finickiness, is a defining feature of the ventromedial hypothalamic (VMH) lesion syndrome. The precise anatomical locus mediating this disturbance has not been determined. This study examines the hypothesis that interruption of amygdalo-hypothalamic connections (either ascending or descending) via the stria terminalis (ST) is involved in VMH lesion-induced finickiness. Taste reactivity was assessed in animals with VMH lesions, ST knife cuts, combined VMH/ST damage, and controls. In sham feeding tests of taste reactivity, ST and VMH rats were equally hyperreactive compared to controls. Rats with combined VMH and ST damage, however, were more reactive than both these groups. None of the brain lesions resulted in an overreactivity to quinine adulteration of the diet. In contrast to sham feeding, ST rats were not hyperphagic when feeding normally, although VMH rats were. In fact, ST damage attenuated VMH-induced hyperphagia and weight gain. We conclude that the taste reactivity changes induced by VMH lesions and ST transections are independent and additive indicating that VMH finickiness does not involve disruption of amygdalo-hypothalamic connections. Nonetheless, disruption of the ST produces a dramatic change in taste reactivity and the properties and origins of this disturbance are discussed.     

B6-MSM Consomic Mouse Strains Reveal Multiple Loci for Genetic Variation in Sucrose Octaacetate Aversion

Based on crosses among inbred strains derived principally from M. m. domesticus, sucrose octaacetate (SOA) aversion in laboratory mice has been thought for many years to be controlled by a single genetic locus (Soa) located on distal chromosome (Chr) 6. To expand knowledge of the genetic basis underlying SOA aversion, we have studied the M. m. molossinus derived strain (MSM) and MSM consomic strains on a M. m. domesticus (C57BL/6J: B6) host background. Using two-bottle preference procedures, MSM mice avoided 0.1?mM and 1?mM SOA while B6 mice were indifferent to 0.1?mM and exhibited slight aversion to 1?mM SOA. Preference tests of 16 available consomic strains implicated Chr 2, 4 and 15 in SOA aversion in addition to the prominent effect of the known Soa locus on Chr 6 (implicated by study of two congenic strains). The originally defined Soa locus is presumably associated with one or more members of the cluster of Tas2r genes on distal Chr 6 that code for bitter taste receptors. Our results point to the possible role of established Tas2r genes on Chr 2 and 15, as well as to genes not coding for bitter receptors (Chr 4), in SOA aversion. SOA aversion emerges from this consomic screen as being definitively under polygenic control. The genetic diversity captured by the MSM model system is shown to be a valuable tool to complement the limited genetic variation in the commonly used stocks derived from M m. domesticus.     

Influence of taste on dietary choice of rats fed amino acid imbalanced or deficient diets

Diets with added quinine as the negative taste cue or saccharin as the positive taste cue were employed to determine the influence of taste on dietary choice of rats offered diets containing different proportions of amino acids (amino acid imbalance) and which differed in acceptability. The quinine was added to the protein-free or the corrected (corrected for amino acid imbalance) diet that animals normally preferred and the saccharine was added to the amino acid imbalanced or deficient diets that animals normally avoided. There appeared to be a balance in acceptance of a diet between the undesirability of the quinine and the degree of metabolic benefit from the diets with favorable metabolic or nutritional characteristics. Although the presence of higher levels of quinine could interfere with the normal dietary preference based on metabolic consequences, the animals invariably selected the metabolically favorable diet if they were forced to experience the metabolic characteristics of the diets by having to consume them exclusively. The presence of the taste cues appeared to enhance the acceptance or avoidance of diets in the choice regimens, possibly by aiding in their identification, especially to animals previously not exposed to the taste cues.     

Sensitive period for the acceptance of unpalatable flavors in the presence of a preexposed odor in infant rats

It has been shown that exposure to familiar odors facilitate the acceptance of bitter flavors in preweanling rats, yet it unknown how long this phenomenon persists. This study assessed, in 9- or 15-day-old Wistar rats, the influence of a familiar scent (i.e., lemon) on the intake of and behavioral responsiveness (i.e., mouthing, paw lick, chin rub, head shake, among other taste reactivity responses) elicited by a 0.1% quinine solution. The results showed heightened quinine intake in 9-day-old rats that had been preexposed to the odor, when compared to non-preexposed controls. This result was replicated in Experiment 2, which also documented no alterations in behavioral responsiveness toward quinine in the 9-day-old rats, as a function of the pre-exposure. More importantly, 15-day-old rats exhibited no alterations in intake or behavioral responsiveness toward quinine as a function of odor pre-exposure. These results suggest that the effects of odor pre-exposure upon acceptance of bitter tastes may occur within a sensitive period for the acceptance of bitter food.     

Facilitation of hypothalamic obesity by greasy diets: Palatability vs lipid content

Rats with obesifying lesions of the ventromedial hypothalamus (VMH), obesifying hypothalamic knife cuts, or sham operations, were given a synthetic powdered high-fat diet and/or an isocaloric and preoperatively preferred synthetic powdered control diet. Postoperatively the knife-cut rats preferred, overate, and became obese on the high fat diet. The electrolytically lesioned rats did not show a switch in preference, but they did overeat and became obese on the synthetic high fat diet when it was the only diet available. Thus, postingestive aspects of high-fat diets contribute to overeating. When a standard Purina chow diet was subsequently presented as pellets instead of as powder, overeating again occurred. In this case preingestive factors alone facilitated feeding. When firm consistency, high fat content, and high caloric density were combined in a Purina/Crisco high fat diet, the greatest intakes and weight gains of all three tested diets were obtained. Thus, both pre- and postingestive changes in response to the diet appear to contribute to the mediation of hypothalamic obesity. These factors not only persist, but are exaggerated in the obesity elicited by hypothalamic knife cuts.     

Alterations of sucrose preference after Roux-en-Y gastric bypass

Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as “just about right” pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p < 0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p = 0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p < 0.05), but both groups considered the same sucrose concentration as “just about right” postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass.     

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.     

Taste reactivity alterations after IL-1beta microinjection into the ventromedial hypothalamic nucleus of the rat

The ventromedial hypothalamic nucleus (VMH) is a central site of action of interleukin-1beta (IL-1beta) induced feeding disturbances. This study was designed to elucidate taste-related perceptual and motivational processes potentially contributing to the anorexia and adipsia seen after bilateral IL-1beta microinjection into the VMH. A saccharin conditioned taste aversion (CTA) paradigm was tested after the central IL-1beta administration. To further investigate whether gustatory deficits are involved in development of the feeding alterations, IL-1beta induced changes of taste responsiveness were also studied in taste reactivity tests. Administration of the cytokine into the VMH did not cause the development of CTA. During taste reactivity tests, however, IL-1beta treated rats displayed significantly poorer ingestive reactions to pleasant taste stimuli than did animals of the control group. In addition, the aversive responses of IL-1beta injected rats to pleasant tastes were significantly more robust than those of control animals. The cytokine treated animals also showed stronger aversion than ingestion to hedonically positive tastes. The present findings indicate that (1) anorexigenic and adipsogenic consequences of IL-1beta microinjection into the VMH are not due to development of cytokine induced CTA; and (2) hedonic responsiveness to palatable tastes is processed by IL-1beta mediated neural mechanisms in the VMH.     

The effect of high fat diet on the behavioral patterns of male rats

Male albino rats were made obese by a high fat diet (40% by weight) initiated either after weaning or at adulthood. The behavioral characteristics of these obese male rats on those tasks which differentiate the VMH lesioned rats from control rats were compared to those of normal rats. It was found that dietary obese male rats were not finicky to quinine adulteration or sugar solution; they did not overreact to shock stimulation by performing better in the shuttle box, and did not drink more “shocked” water. The behavior of dietary obese male rats did not differ from normals in activity level and in food motivated operant behavior. No behavioral differences between early and late onset obese groups were found. The discrepancy in results between the present experiment and those previously reported and the possible physiological background are discussed.     

Effects of central amygdaloid nucleus lesions on ingestion, taste reactivity, exploration and taste aversion.

Central amygdaloid nucleus lesions in rats had no effect on recovery of preoperative body weight and food consumption levels. The brain damaged rats also recovered preoperative levels of water consumption as rapidly as control rats but then developed a mild but persistent hypodipsia. The experimental rats also drank less than control rats when food deprived and showed marginally reliable decreases in 0.1% quinine solution consumption and latency to consume a novel food. There was no detectable lesion effect on 0.1% saccharin solution consumption, exploration of a novel environment or formation of a learned taste aversion. It is suggested that the central amygdaloid nucleus has a role in mediating the relationship between food and water intake and in some taste mediated consummatory behavior.     

Effects of body weight loss and taste on VMH-LH electrical activity of rats.

Electrical responses of ventromedial (VMH) and lateral (LH) hypothalamus to graded decrease in body weight and to taste were recorded from a conscious rat with chronically implanted macroelectrodes. Graded reduction in body weight was correlated with gradual increase in LH activity and reciprocal decrease in VMH activity, both of which were stable and specific to each gradation in body weight. On gustation of any test solution, basal activity was temporarily altered, if any. On sweet taste of calorically rich sucrose, VMH activity was enhanced and LH showed decrease. But on sweet taste of calorically inert saccharin, VMH activity was increased, though a reciprocal decrease in LH was not shown. Contrastingly, both bitter taste and salt taste caused increased LH activity but no change in VMH activity. Enhanced VMH activity correlated with sweet taste may be due to activation of VMH glucoreceptors. LH activation correlated with bitter and salt taste is a likely response of two distinct groups of LH units; one responding to salt taste and the other to bitter aversive taste.     

Morphine- and naltrexone-induced modification of palatability: analysis by the taste reactivity test.

We used the taste reactivity (TR) test, a direct measure of the hedonic properties of a tastant, to assess in Sprague-Dawley rats the ability of morphine (an opiate agonist) and naltrexone (an opiate antagonist) to modify the palatability of a bitter quinine solution and a sweet sucrose solution. Morphine reduced the aversive hedonic properties of both novel and familiar quinine solution (0.05% and 0.1%) but did not modify the palatability of 20% sucrose solution. Naltrexone reduced the positive hedonic properties of sucrose solution (2% and 20%) but did not modify the palatability of 0.05% quinine solution. The pattern of results suggests that the modification of feeding produced by opiate agonists and antagonists may be mediated by an hedonic shift in the palatability of the tastant.