Effect of delta9-tetrahydrocannabinol on quinine palatability and AM251 on sucrose and quinine palatability using the taste reactivity test

Here we provide evidence that the cannabinoid agonist, Delta9-tetrahydrocannabinol (Delta9-THC) enhances quinine palatability and the CB1 antagonist/inverse agonist, AM251, reduces sucrose and quinine palatability using the taste reactivity test, which provides a direct measure of palatability independently of appetitive behavior. In Experiment 1, rats were treated with a low dose of Delta9-THC (0.5 mg/kg) or Vehicle 30 min, 60 min, 120 min or 240 min prior to a 5-min intraoral infusion of a highly unpalatable 0.05% quinine solution. Regardless of the post-injection interval, Delta9-THC reduced rejection of quinine. The Delta9-THC-induced palatability shift was reversed by AM251. In Experiment 2, rats were injected with either AM251 (1 mg/kg) or Vehicle prior to receiving a 5-min intraoral infusion of either 32% sucrose or 0.05% quinine solution. AM251 significantly decreased sucrose-elicited hedonic reactions across both time intervals; however, AM251 did not significantly modify the rejection of 0.05% quinine solution. When the concentration of the quinine solution was reduced to 0.01% in Experiment 3, AM251 enhanced quinine aversion. Although the range of concentrations of the solutions tested in the present data is limited, our results suggest that the cannabinoid system may modulate the palatability of ingested substances regardless of the palatability of the ingested substance.     

Taste avoidance, but not aversion, learning in rats lacking gustatory cortex.

Control rats rapidly learned to avoid drinking either a sucrose solution (Experiment 1) or a NaCl solution (Experiment 2) when the taste was paired with illness. These rats also produced aversive reactivity to each of these solutions in a taste reactivity test. Rats that lacked gustatory cortex (GC) learned to avoid drinking sucrose and NaCl, albeit at a slower rate than control rats. GC rats failed to display aversive reactivity to these tastes. The GC rats did show normal aversive reactivity to a strong quinine HCl solution during additional tests. It is suggested that the avoidance developed by GC rats did not entail a palatability shift of the conditional stimulus as it did in control rats. This altered learning strategy may account for the consistent learning deficits found in GC rats trained to avoid tastes.     

Ondansetron and Delta-9-tetrahydrocannabinol interfere with the establishment of lithium-induced conditioned taste avoidance in the house musk shrew (Suncus murinus)

Considerable evidence suggests that rats can learn to avoid a taste in the absence of nausea. The current experiments evaluated the potential of the antiemetic agents, ondansetron (OND) and delta-9-tetrahydrocannabinol (THC), to interfere with lithium chloride (LiCl)-induced taste avoidance in the house musk shrew, Suncus murinus, an insectivore that, unlike rats, is capable of vomiting. At a dose that did not modify saccharin (Experiment 1) or sucrose (Experiment 2) intake, OND prevented the establishment of LiCl-induced taste avoidance in the shrew. A low dose of THC (1 mg/kg), which did not modify sucrose intake during conditioning, also prevented the establishment of LiCl-induced taste avoidance in the shrew. Higher doses of THC were also effective, but they also suppressed sucrose consumption during conditioning. These results suggest that nausea is a necessary component of the unconditioned stimulus for the establishment of conditioned taste avoidance in the shrew, unlike the rat, which does not vomit when injected with a toxin.     

Taste preference and acceptance in thirsty and rehydrated [correction of 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.     

Effect of conditioning method and testing method on strength of lithium-induced taste aversion learning

Here the authors evaluated the effect of the method of conditioning (bottle or intraoral [IO] infusion) on the strength of a flavor-drug association when measured in a standard 1-bottle consumption test or when measured by IO infusion in a taste reactivity test. When tested with the bottle test in Experiment 1, rats conditioned by bottle displayed stronger taste avoidance than those conditioned by IO infusion. When tested for rejection reactions with the taste reactivity test in Experiment 2, rats conditioned by infusion displayed a stronger aversion than did rats conditioned by bottle. The results suggest that when the contextual cues of conditioning are similar at conditioning and testing, a stronger association is evident regardless of the individual specifics of each method. These results may shed light on recent reports that different neural mechanisms are involved in conditioning by active consumption and passive infusion.     

Differential effects of removing the glucose or saccharin components of a glucose-saccharin mixture in a successive negative contrast paradigm

When rats experience an unexpected decrease in reward value, e.g., from 32% sucrose to 4% sucrose, consummatory behavior abruptly decreases to a level below control subjects that only experience the lesser reward, a phenomenon known as Successive Negative Contrast (SNC). In food deprived rats experiencing downshifts in sucrose concentration, SNC dissipates in 3-4 days, as consummatory behavior in shifted rats recovers to the level of unshifted controls. In Experiment 1 food deprived rats that were given 5 min daily access to a 2% glucose-0.15% saccharin mixture, and subsequently shifted to 2% glucose alone, displayed a dramatic SNC effect relative to rats that only received 2% glucose. This SNC effect was primarily manifested as a decrease in the number of consummatory bursts initiated. Interestingly, intake failed to recover to control levels during eight daily postshift sessions. However, in Experiment 2 subjects that were shifted from the same glucose-saccharin mixture to 0.15% saccharin alone failed to show SNC rather, intake fell to the level of control animals which only received 0.15% saccharin. The data from Experiment 1, in conjunction with previous studies utilizing non-deprived rats, quinine adulteration, or shifts from sucrose to saccharin, show that reductions in taste value can produce contrast effects, but suggest that a threshold caloric value is necessary for recovery. The data from Experiment 2 may suggest that saccharin and glucose do not contribute equally to the enhanced palatability of the mixture.     

Taste reactivity as a dependent measure of the rapid formation of conditioned taste aversion: a tool for the neural analysis of taste-visceral associations

Several explanations may account for deficits in the ability of animals to form taste aversions following neural manipulations. These encompass impairments in conditioned stimulus (CS) and unconditioned stimulus (US) processing, conditioned response (CR) measurement, and expression, memory, and taste-visceral integration. A behavioral procedure that aids in the distinction between some of these possibilities is presented. In Experiment 1, 10 rats received seven intraoral (IO) infusions of sucrose (30 s, 0.55 ml) spaced every 5 min starting immediately after the injection of 3.0 mEq/kg of lithium chloride (LiCl). Control rats (n = 12) were treated identically except that they were injected with sodium chloride (NaCl). Oromotor and somatic taste reactivity behaviors were videotaped and analyzed. Lithium-injected rats systematically decreased their ingestive taste reactivity behavior over time, whereas aversive behavior increased. Control rats maintained high and stable levels of ingestive responding and demonstrated virtually no aversive behavior over the 30-min period following sodium injection. Rats were tested several days later for the presence of a conditioned taste aversion (CTA). Rats previously injected with lithium during sucrose infusions demonstrated significantly more aversive behavior than the control group, which demonstrated none. There were no differences in the level of ingestive behavior displayed by the two groups on the CTA test. Experiment 3 revealed that when similarly treated rats were tested for a CTA while in a lithium-induced state, a difference in the ingestive behavior between the two groups was observed. In Experiment 2, naive rats were injected with either NaCl or LiCl but did not receive their first sucrose infusion until 20 min later. These rats also received sucrose infusions at 25 and 30 min postinjection. There were no differences in the taste reactivity behavior displayed by lithium- or sodium-injected rats during any of the sucrose infusions. Collectively, these findings indicate that rats dramatically change their oromotor responses to sucrose during the period following LiCl administration, provided that the infusions start immediately after injection. Furthermore, this time-related behavioral change is predominantly attributable to associative processes. This paradigm can be useful in distinguishing between neural manipulations that affect the establishment of taste-visceral associations from others that affect the animal's ability to retain such associations over the commonly employed 24-hr conditioning-test interval.     

Enhanced sucrose and Polycose preference in sweet "sensitive" (C57BL/6J) and "subsensitive" (129P3/J) mice after experience with these saccharides

Prior research with inbred mouse strains indicates that C57BL/6J (B6) mice display stronger preference and acceptance for various sweeteners than do 129P3/J (129) mice. Experiment 1 examined the extent to which this strain difference could be modified by repeated exposure to sucrose. Sucrose-naive 129 mice displayed weaker preferences than did B6 mice for 0.5% to 4% sucrose solutions during 23h/day sugar vs. water tests. Sucrose preference did not differ at 8-32% concentrations. Yet, when retested with sucrose, the 129 and B6 mice showed identical robust preferences (>90%) for 0.5-32% solutions. The strains also did not differ in sucrose preference in tests with descending sucrose concentrations (0.5-0.0625%). Sucrose-experienced 129 mice also showed enhanced preference for dilute saccharin solutions suggesting that their sweet taste responsivity was enhanced. Experiment 2 revealed that preference for dilute saccharin solutions was enhanced by prior saccharin experience in B6 but not 129 mice. Experiment 3 tested the strains with Polycose which has a palatable taste different from that of sucrose. Polycose-naive 129 mice displayed weaker preferences for dilute (0.5-4%) but not concentrated (8-32%) Polycose solutions relative to B6 mice. In the second test series Polycose preferences were nearly identical in the two strains. In Experiments 1 and 3, prior sucrose or Polycose experience also reduced or eliminated strain differences in saccharide acceptance (absolute intake) at higher but not lower concentrations. Thus, exposure to the oral and post-oral actions of sucrose and Polycose increased saccharide preference in B6 mice and even more in 129 mice so that the strain difference virtually disappeared. Whether the 129 mice responded to the taste or other properties (e.g., odor) of the dilute saccharide solutions is not certain but their gustatory sensitivity needs to be reconsidered.     

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.     

Evaluation of the 'liking' and 'wanting' properties of umami compound in rats

Food reward is neurologically and psychologically divided into at least two properties; ‘liking’ and ‘wanting’. Although umami taste enhances food palatability, the liking and wanting properties of umami taste, and the underlying neural mechanisms for these properties are not clear. Here, we compared sucrose (0, 10, 30, 120 and 480 mM) and monosodium l-glutamate (MSG; 0, 10, 30, 60 and 120 mM) solutions using a taste reactivity test to evaluate liking, and fixed/progressive-ratio operant licking tasks to evaluate wanting. To determine the underlying neural mechanisms, we also conducted systemic blockade of opioid receptors in both tests. In the taste reactivity test, the hedonic reactions to 30, 60 and 120 mM MSG were greater than those to water (0 mM) but lower than those to 480 mM sucrose. In the operant task, the intake, number of licks, and breakpoint to MSG reached peaks at around 60 mM but they were lower than those to 30-480 mM sucrose. The systemic naloxone treatment decreased the hedonic responses to MSG and sucrose, and reduced the incentive salience of MSG but not sucrose. These findings indicate that the hedonic response and incentive salience of MSG is lower than those of sucrose when compared at the maximum response and that the incentive salience of MSG is lower than sucrose even where the hedonic response is similar. The present study also suggest that the hedonic response and incentive salience of umami compound is modulated by brain opioid signaling.     

Conditioned acceptance and preference but not altered taste reactivity responses to bitter and sour flavors paired with intragastric glucose infusion

Nutrient-conditioned flavors preferences are thought to involve an increase in flavor palatability (hedonic evaluation). Consistent with this view is the recent finding that a sweet flavor paired with intragastric glucose infusions elicited more hedonic taste reactivity (TR) responses than did an alternative sweet flavor paired with intragastric water. The generality of this finding was examined by conditioning preferences for inherently avoided nonsweet flavors. Rats were trained in 20 h/day and then 30 min/day sessions with a CS+ flavor (sour citric acid or bitter sucrose octaacetate) paired with intragastric 16% glucose infusion, and the opposite flavor (CS-) paired with intragastric water. Glucose conditioning increased the CS+ acceptance in one-bottle tests and produced a 95% CS+ preference in two-bottle sessions. Yet, TR responses to brief intraoral infusions of the two CS flavors did not differ, even after extensive testing. Subsequent choice tests revealed that a 1% fructose solution was preferred to the CS-, whereas the CS+ was preferred to 1% and 2% fructose and equally preferred to 4%, 8%, and 16% fructose. These results indicate that strong nutrient-conditioned flavor preferences are not always associated with increased flavor palatability as measured by TR tests. Therefore, nonhedonic processes, perhaps increased incentive salience, appear to mediate the enhanced preference and acceptance conditioned by postingestive nutrient actions.     

Sucrose motivation in sweet "sensitive" (C57BL/6J) and "subsensitive" (129P3/J) mice measured by progressive ratio licking

As compared to C57BL/6J mice, 129P3/J mice show weaker preferences for and lower intakes of dilute sugar solutions. These differences have been attributed to genetic differences in their sweet taste receptor. The two mouse strains do not differ, however, in their intake of concentrated sugar solutions. The post-oral satiating effect of concentrated sugar solutions may mask strain differences in the avidity for these solutions. This hypothesis was investigated using fixed ratio (FR, low demand) and progressive ratio (PR, high demand) operant licking tests (22h/day) to measure sugar appetite. In Experiment 1, sucrose-experienced 129 mice licked less than did B6 mice for 4% but not for 16% sucrose in free access bottle tests and FR operant tests. Yet, in PR tests the 129 mice licked as much for 4% sucrose and more for 16% sucrose than did B6 mice. In Experiment 2, sucrose-naive 129 mice licked less than did B6 mice in FR and PR tests with 0.4% saccharin but the strains did not differ in PR licking in their first test with 16% sucrose. After they were given unconstrained bottle access to 16% sucrose for 3 days, the 129 mice now licked more than B6 mice in a second sucrose PR test. Thus, despite having a less sensitive sweet taste receptor, 129 mice are as much or more motivated to obtain sucrose than are B6 mice and appear to be more influenced by prior experience with sugar. This suggests that the strains differ in their central reward processing of sweet taste.     

Rats learn to like the taste of morphine

When rats are forced to drink a morphine solution as their only source of fluid, they eventually reverse their initial preference and drink more morphine than water in a two-bottle preference test. The cause of this shift in preference was examined with the taste reactivity test which involves the analysis of fixed action patterns elicited by taste solutions infused into rats' mouths. Three morphine concentrations and two levels of motivation were studied. A greater percentage of ingestive taste reactivity responses occurred to the oral morphine infusion in morphine-raised rats than in water-raised rats. These data argue against the idea that enhanced morphine ingestion is caused by anticipation of positive consequences. Instead, they support the idea that rats come to "like" the flavor of the morphine solution; in other words, the palatability evaluation of the morphine changes, possibly through an association between the flavor and the hedonically positive effects of the morphine.     

The role of T1r3 and Trpm5 in carbohydrate-induced obesity in mice

We examined the role of T1r3 and Trpm5 taste signaling proteins in carbohydrate-induced overeating and obesity. T1r3, encoded by Tas1r3, is part of the T1r2+T1r3 sugar taste receptor, while Trpm5 mediates signaling for G protein-coupled receptors in taste cells. It is known that C57BL/6 wild-type (WT) mice are attracted to the tastes of both Polycose (a glucose polymer) and sucrose, whereas Tas1r3 KO mice are attracted to the taste of Polycose but not sucrose. In contrast, Trpm5 KO mice are not attracted to the taste of sucrose or Polycose. In Experiment 1, we maintained the WT, Tas1r3 KO and Trpm5 KO mice on one of three diets for 38days: lab chow plus water (Control diet); chow, water and 34% Polycose solution (Polycose diet); or chow, water and 34% sucrose solution (Sucrose diet). The WT and Tas1r3 KO mice overconsumed the Polycose diet and became obese. The WT and Tas1r3 KO mice also overconsumed the Sucrose diet, but only the WT mice became obese. The Trpm5 KO mice, in contrast, showed little or no overeating on the Sucrose and Polycose diets, and gained less weight than WT mice on these diets. In Experiment 2, we asked whether the Tas1r3 KO mice exhibited impaired weight gain on the Sucrose diet because it was insipid. To test this hypothesis, we maintained the WT and Tas1r3 KO mice on one of two diets for 38 days: chow, water and a dilute (1%) but highly palatable Intralipid emulsion (Control diet); or chow, water and a 34% sucrose+1% Intralipid solution (Suc+IL diet). The WT and Tas1r3 KO mice both exhibited little or no overeating but became obese on the Suc+IL diet. Our results suggest that nutritive solutions must be highly palatable to cause carbohydrate-induced obesity in mice, and that palatability produces this effect in part by enhancing nutrient utilization.     

Conditioned enhancement of flavor evaluation reinforced by intragastric glucose. II. Taste reactivity analysis.

Rats learn to prefer a flavor that is paired with intragastric (IG) glucose infusion, which may represent a learned shift in the hedonic evaluation or palatability of the flavor. The present study used the taste reactivity (TR) test to infer nutrient-conditioned changes in flavor palatability. Rats were first conditioned in 20-h/day and then 30-min/day sessions to associate a flavored saccharin solution (the CS+) with IG infusions of 16% glucose, and a different flavored saccharin solution (the CS-) with IG water infusions. They strongly preferred the CS+ to the CS- in two-bottle intake tests. When next tested with brief intraoral (IO) infusions of the CS flavors, the rats exhibited significantly more hedonic TR responses to the CS+ flavor than the CS- flavor, which indicates an enhanced hedonic evaluation. A subsequent series of two-bottle tests established that the CS- flavor was equally preferred to 3% fructose, whereas the CS+ flavor was equally preferred to 16% fructose. In addition, the difference between the TR responses to 3% and 16% fructose paralleled the difference between the TR responses to CS- and CS+. These findings support the idea that pairing flavored saccharin with the postingestive effects of glucose produces a learned shift in palatability comparable to that produced by increasing the concentration of a sugar solution.     

Effects of number of pre-exposures on sucrose taste aversion in weanling rats

Weanling rats, 20 days old, received 0, 1, 2, 4, or 8 pre-exposures to 12% sucrose prior to a single pairing of sucrose with an intraperitoneal injection of lithium chloride (LiCl; 3.0 mEq of a .15Msolution) or distilled water (20 mg/kg). Testing for sucrose taste aversion with a 2-bottle-choice procedure on 9 test trials reliably showed that increasing numbers of pre-exposures to sucrose directly attenuated taste aversion effects in the LiCl-injected groups but did not appreciably affect intake performance in the distilled water-injected groups. Comparisons between the injection conditions yielded reliable evidence for sucrose taste aversion at each pre-exposure level. These results show that flavor stimulus pre-exposures reliably attenuate subsequent taste aversion in weanling rats as had previously been reported for adult rats.     

A quantitative comparison of taste reactivity behaviors to sucrose before and after lithium chloride pairings: a unidimensional account of palatability.

Alterations in the motivation to ingest sucrose can be quantified by measuring the number and type of oral motor and somatic responses (i.e., taste reactivity [TR]) that are elicited by sucrose. In 2 experiments, rats had intraorally infused sucrose paired with LiCl injections for several trials, or they were injected with LiCl and had sucrose infused every 5 min during the 30-min postinjection period (data from Spector, Breslin, & Grill, 1988). In both experiments, ingestive TR responses decreased, whereas aversive TR responses increased over trials. Individual response components that comprise the ingestive and aversive categories followed the same trends of increase or decrease but changed at different rates as a function of number of trials or exposures. Overall, the array of response components could be projected onto a single unidimensional scale of palatability to capture the motivational states that ranged from acceptance to rejection.     

Intake inhibition by NPY: role of appetitive ingestive behavior and aversion

Intraventricular infusion of neuropeptide Y (NPY) decreases the amount female rats ingest during intraoral infusion (consummatory behavior) of a 1-M solution of sucrose at a rate of 0.5 ml/min and simultaneously increases the number of times the rats visit a bottle filled with sucrose (appetitive behavior). In this study, we investigated if the suppression of consummatory behavior was dependent upon the increase of appetitive behavior. The shift from consummatory to appetitive ingestive behavior was attenuated by adding 3-mM quinine HCl (QHCl) to the sucrose solution in the bottle. However, the intraoral intake of the sucrose solution was still decreased in NPY-treated rats. NPY did not modify taste reactivity as measured by aversive responses during continuous intraoral infusion of sucrose or ingestive and aversive responses to brief intraoral infusion of sucrose (0, 0.3 or 1 M) or QHCl (0, 0.3 or 3 mM). NPY stimulated visits to a bottle and intake from the bottle and inhibited sexual behavior in male rats but had no effect on the sexual behavior in the absence of a bottle. The visits and the intake were suppressed, but sexual behavior was not activated by adding QHCl (3 mM) to the solution in the bottle. Obstructing appetitive ingestive behavior, therefore, does not indiscriminately facilitate consummatory behavior. Male rats showed aversive or ingestive behavior and sexual behavior simultaneously during intraoral infusion of QHCl or condensed milk. It is suggested that NPY decreases intraoral intake and increases appetitive ingestive behavior via partially separable mechanisms that are independent of taste aversion.     

Ethanol palatability and consumption by high ethanol-drinking rats: manipulation of the opioid system with naltrexone

Three experiments examined the effect of acute naltrexone treatment on both taste reactivity and consumption of ethanol in high ethanol-preferring rat lines: Alko Alcohol-Accepting (AA) rats (Experiments 1 and 2) and Alcohol-Preferring (P) rats (Experiment 3). A 3.0 mg/kg naltrexone dose was ineffective at altering ethanol palatability for either line, whereas 7.5 mg/kg was effective at reducing palatability of 10% ethanol for AA, but not P, rats, as reflected by both a decrease in ingestive responding and an increase in aversive responding. The effects of naltrexone on ethanol consumption were quite consistent: At both dosages, acute naltrexone treatment significantly decreased consumption of 10% ethanol. Termination of naltrexone resulted in an immediate increase in ethanol consumption to control levels. Results show that ethanol palatability and consumption can be dissociated in the rat and that the organization of opioidergic mechanisms that mediate ethanol responses may vary between rat lines.