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Drug taste, which affects palatability, influences drug adherence. Sensory masking may be used to confound bitter tastes in drugs with other tastes and flavors; however, evaluation of sensory masking is difficult because of the existence of multiple tastes. In this study, a new two-bottle choice test was performed in rats to evaluate bitterness masking and determine the drug-to-sweetener ratio that significantly improves palatability. Sulfamethoxazole and trimethoprim were used as model bitter drugs, and sucralose was used as sweetener. The addition of sucralose and trimethoprim at a 0.13 : 1 ratio resulted in the greatest improvement in preference. This method is a useful new technique for evaluating the palatability of drug formulations.

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The development of excessive alcohol (ethanol) and/or highly palatable food self-administration is an essential task to elucidate the neurobiological mechanisms that underlie these behaviors. Previous work has highlighted that ethanol self-administration is modulated by both the induction of aversive states (i.e., stress or frustration) and by the concurrent availability of appetitive stimuli (e.g., food). In our protocol, rats are food deprived for three days until they reach 82%-85% of their ad libitum weight. After that, rats are exposed daily for 10 days to a brief binge or control eating experience with highly sugary and palatable food (i.e., the ingestion of 11.66 and 0.97 kcal/3 min, respectively), which is followed by a two-bottle-choice test (ethanol vs. water) in their home cages for 90 min. This model induces robust binge eating, which is followed by a selective increase in ethanol self-administration. Therefore, this protocol allows to study: a) behavioral and neurobiological factors related to binge eating, b) different stages of alcohol use, and c) interactions between the latter and other addictive-like behaviors, like binge eating.

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Dried bonito dashi, a complex mixture of sour, bitter, and umami substances as well as over 400 odorants, is the most widely used Japanese fish broth that enhances palatability of various dishes. Recent studies have suggested that prior experience with dried bonito dashi produces strong enhancement of subsequent intake and preference for dried bonito dashi. The present study investigated taste substances in dried bonito dashi that enhance subsequent dashi preference by its prior exposure. Male C57BL/6N mice were initially exposed for 10 days to (1) dried bonito dashi, (2) a chemical mixture of taste substances identified in dried bonito dashi (artificially reconstituted dashi), or (3) individual chemical solutions such as NaCl, monosodium l-glutamate (MSG), inosine 5'-monophosphate (IMP), lactic acid, histidine, and glucose. Intakes of 0.01-100% dried bonito dashi with water were then measured using ascending concentration series of 2-day two-bottle choice tests. Prior exposure to 1-100% dashi enhanced subsequent dashi preference in a concentration-dependent manner and the greatest effects were attained with 10-100% dashi exposure. Exposure to the reconstituted dashi also enhanced subsequent dashi preference. Among individual chemical solutions, 0.1% IMP produced modest enhancement of subsequent dashi preference, but neither NaCl, MSG, histidine, lactic acid, nor glucose did. These results suggest that IMP is at least a key substance that produces experience-based enhancement of dried bonito dashi preference.

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Dried bonito dashi is a traditional Japanese fish broth that enhances palatability of various dishes due to its specific flavor. The present study examined influences of dietary fat levels (10% vs. 45% fat), presentation order of dried bonito dashi (ascending vs. descending concentrations), and prior experience with dashi on subsequent dashi intake and preference using two-bottle choice tests in two rodent strains, Sprague-Dawley (SD) rats and C57BL/6 N (B6N) mice. In the ascending concentration tests, SD rats on a low fat diet preferred 10-100% dashi to water, whereas B6N mice showed a blunted preference for dashi. Consumption of a high fat diet reduced dashi preference in SD rats. The B6N mice on the high fat diet never preferred dashi at any concentration. In the descending concentration tests, SD rats on the low fat diet preferred dashi over a wide range (0.03-100% dashi). The B6N mice showed a trend similar to that of SD rats. Ingestion of the high fat diet in both strains reduced dashi preference in the descending concentration tests. However, introduction of the high fat diet to dashi experienced rats maintained on the low fat diet, reduced neither dashi intake nor dashi preference. Dashi intake affected neither high fat diet intake, caloric intake, nor preference for high fat diet. These results suggest that preference for dried bonito dashi is influenced at least by 1) dietary fat levels, 2) presentation order of dashi, and 3) prior experience with dashi.

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Maternal high-fat (HF) diet affects offspring's metabolic phenotype. Sweet taste is an important factor in promoting appetite. In order to determine the effects of maternal HF diet throughout gestation and lactation on taste sensitivity to sucrose in rat offspring, we measured conditioned aversion threshold for sucrose by conditioned taste aversion (CTA) associated with two-bottle choice tests, and measured mRNA expression of sweet taste receptors in taste buds. In male offspring, conditioned aversion threshold for sucrose lay between 0.007 M and 0.009 M in control group, while in those with HF dams, the threshold significantly increased to be between 0.011 M and 0.02 M. In female offspring, conditioned aversion threshold for sucrose lay between 0.003 M and 0.005 M in control group, whereas maternal HF diet increased it to be between 0.007 M and 0.009 M. Maternal HF diet increased T1R2 and T1R3 mRNA expression in taste buds of male offspring, while only increased T1R2 mRNA expression in female offspring. Both male and female offspring with HF dams had lower α-gustducin mRNA expression, whereas only male offspring with HF dams had lower OB-Rb mRNA expression in taste buds. Our data suggest that maternal HF diet decreased taste sensitivity to sucrose in both male and female offspring, which may be partly due to altered expression of sweet taste receptors and related downstream pathways in taste buds.

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Preclinical data indicate that ethanol produces behavioral effects that can be regulated by many neurotransmitters and neuromodulators like adenosine (A). The most important receptors with respect to the rewarding effects of ethanol seem to be the A2A receptors. This study used a transgenic strategy, specifically rats overexpressing the A2A receptor, to characterize the neurobiological mechanisms of ethanol consumption as measured by intermittent access to 20% ethanol in a two-bottle choice paradigm. In this model, no change in ethanol consumption was observed in transgenic animals compared to wild type controls during the acquisition/maintenance phase. Following alcohol deprivation, only transgenic rats overexpressing the A2A receptor exhibited escalation of ethanol consumption and drank more (by ca. 90%), but not significantly, ethanol than did the wild type rats. During ethanol withdrawal, the immobility time of rats overexpressing the A2A receptor in the forced swim test was lower than that of wild type rats. Moreover, transgenic rats withdrawn from ethanol, compared to the drug-naive transgenic animals, exhibited an increase above 70% in locomotion. The results indicated that the overexpression of A2A receptors may be a risk factor for the escalation of ethanol consumption despite the reduction in depression-like signs of ethanol withdrawal.

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To investigate the appetite for vitamin C (VC), we conducted behavioral and neural experiments using osteogenic disorder Shionogi/Shi Jcl-od/od (od/od) rats, which lack the ability to synthesize VC, and their wild-type controls osteogenic disorder Shionogi/Shi Jcl- +/+ (+/+) rats. In the behavioral study, rats were deprived of VC for 25 days and then received two-bottle preference tests with a choice between water and 10 mM VC. The preference for 10 mM VC solution of od/od rats was significantly greater than that of +/+ rats. In the neural study, the relative magnitudes of the whole chorda tympani nerve (CTN) responses to 100-1000 mM VC, 3-10 mM HCl, 100-1000 mM NaCl, and 20 mM quinine▪HCl in the VC-deficient rats were significantly smaller than those in the nondeficient ones. Further, we conducted additional behavioral experiments to investigate the appetite for sour and salty taste solutions of VC-deficient od/od rats. Preference scores for 3 mM citric acid increased in od/od rats after VC removal, compared with before, whereas preference scores for 100 and 150 mM NaCl were decreased in VC-deficient od/od rats. The preference for 300 mM NaCl was not changed. Hence, our results suggest that the reduction of the aversive taste of VC during VC deficiency may have involved the reduction of CTN responses to acids. Overall, our results indicate that VC-deficient rats ingest sufficient VC to relieve their deficiency and that VC deficiency causes changes in peripheral sensitivity to acids, but nongustatory factors may also affect VC intake and choice.

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Taste compounds detected by G protein-coupled receptors on the apical surface of Type 2 taste cells initiate an intracellular molecular cascade culminating in the release of ATP. It has been suggested that this ATP release is accomplished by pannexin 1 (PANX1). However, we report here that PANX1 knockout mice do not differ from wild-type controls in response to representative taste solutions, measured using 5-s brief-access tests or 48-h two-bottle choice tests. This implies that PANX1 is unnecessary for taste detection and consequently that ATP release from Type 2 taste cells does not require PANX1.

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