Pharmacologic Antagonism of the Oral Aversive Taste-Directed Response to Capsaicin in a Mouse Brief Access Taste Aversion Assay

Long, Daniel; Devantier, Heather R.; Brennan, Francis X.; Bryant, Robert W.; Salemme, F. R.; Palmer, R. Kyle

doi:10.1124/jpet.109.155416

Cited by 13 publications

(17 citation statements)

References 38 publications

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“…Testing for palatability has best been accomplished by brief-access assays that use the Davis Rig [37], an automated lickometer that can present up to 16 sipper tubes to a rodent. Full concentration–response functions for lick rates can be obtained within a 30-minute test session using this method [14,15,22,38]. Since subjects usually are water-deprived, basal lick rates for water are relatively high making assessment of appetitive solutions difficult in brief-access assays [22,39].…”

Section: Discussionmentioning

confidence: 99%

“…Some of these shortcomings have been circumvented by the development of reliable animal models to study complex emergent taste functions [1,7]. These models fall into two general categories: taste discrimination experiments that quantify taste quality [8–11], and studies of “taste-guided” behavior which provide measures of palatability [12–15]. …”

Section: Introductionmentioning

confidence: 99%

“…The lick rates elicited by tastants are compared to those for water, yielding a measure of relative appetitiveness [21] or aversiveness [15]. Since animals usually must be fluid-deprived to motivate them to sample from the tubes, high basal lick rates for water often greatly reduce the window available for measuring tastant appetitiveness [22].…”

Section: Introductionmentioning

confidence: 99%

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A High Throughput In Vivo Assay for Taste Quality and Palatability

Palmer¹,

Long²,

Brennan³

et al. 2013

PLoS ONE

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Taste quality and palatability are two of the most important properties measured in the evaluation of taste stimuli. Human panels can report both aspects, but are of limited experimental flexibility and throughput capacity. Relatively efficient animal models for taste evaluation have been developed, but each of them is designed to measure either taste quality or palatability as independent experimental endpoints. We present here a new apparatus and method for high throughput quantification of both taste quality and palatability using rats in an operant taste discrimination paradigm. Cohorts of four rats were trained in a modified operant chamber to sample taste stimuli by licking solutions from a 96-well plate that moved in a randomized pattern beneath the chamber floor. As a rat’s tongue entered the well it disrupted a laser beam projecting across the top of the 96-well plate, consequently producing two retractable levers that operated a pellet dispenser. The taste of sucrose was associated with food reinforcement by presses on a sucrose-designated lever, whereas the taste of water and other basic tastes were associated with the alternative lever. Each disruption of the laser was counted as a lick. Using this procedure, rats were trained to discriminate 100 mM sucrose from water, quinine, citric acid, and NaCl with 90-100% accuracy. Palatability was determined by the number of licks per trial and, due to intermediate rates of licking for water, was quantifiable along the entire spectrum of appetitiveness to aversiveness. All 96 samples were evaluated within 90 minute test sessions with no evidence of desensitization or fatigue. The technology is capable of generating multiple concentration–response functions within a single session, is suitable for in vivo primary screening of tastant libraries, and potentially can be used to evaluate stimuli for any taste system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A High Throughput In Vivo Assay for Taste Quality and Palatability

Palmer¹,

Long²,

Brennan³

et al. 2013

PLoS ONE

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“…Since different TRPV1 antagonists exhibit different potencies for inhibiting piperine-induced oral aversiveness in rats [25], we used three different TRPV1 antagonists to rule out differences in antagonist potency and receptor affinity as possible confounding factors. All three TRPV1 antagonists failed to interfere with the inhibitory effect of piperine on HUVEC proliferation.…”

Section: Discussionmentioning

confidence: 99%

Piperine, a dietary phytochemical, inhibits angiogenesis

Doucette

Hilchie

Liwski

et al. 2013

The Journal of Nutritional Biochemistry

104

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Angiogenesis plays an important role in tumor progression. Piperine, a major alkaloid constituent of black pepper, has diverse physiological actions including killing of cancer cells; however, the effect of piperine on angiogenesis is not known. Here we show that piperine inhibited the proliferation and G(1)/S transition of human umbilical vein endothelial cells (HUVECs) without causing cell death. Piperine also inhibited HUVEC migration and tubule formation in vitro, as well as collagen-induced angiogenic activity by rat aorta explants and breast cancer cell-induced angiogenesis in chick embryos. Although piperine binds to and activates the cation channel transient receptor potential vanilloid 1 (TRPV1), its effects on endothelial cells did not involve TRPV1 since the antiproliferative effect of piperine was not affected by TRPV1-selective antagonists, nor did HUVECs express detectable TRPV1 mRNA. Importantly, piperine inhibited phosphorylation of Ser 473 and Thr 308 residues of Akt (protein kinase B), which is a key regulator of endothelial cell function and angiogenesis. Consistent with Akt inhibition as the basis of piperine's action on HUVECs, inhibition of the phosphoinositide-3 kinase/Akt signaling pathway with LY-294002 also inhibited HUVEC proliferation and collagen-induced angiogenesis. Taken together, these data support the further investigation of piperine as an angiogenesis inhibitor for use in cancer treatment.

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“…In some articles it is even more inappropriate when the "lick ratios" were calculated by dividing the mean number of licks from each concentration by the mean number of licks from water (7,11,12,19,20 Although some published models exist to analyse the BATA data, these models can only handle data presented in the form of "lick ratios" and most of their parameters are not interpretable. As shown in the results, the proposed E max model can analyse both "lick numbers" and "lick ratios" and the model parameters from these two kinds of data were similar.…”

Section: Discussionmentioning

confidence: 99%

Development of a model for robust and exploratory analysis of the rodent brief-access taste aversion data

Soto

Sheng

Standing

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DEVELOPMENT OF A MODEL FOR ROBUST AND EXPLORATORY ANALYSIS OF THE RODENT BRIEF-ACCESS TASTE ABSTRACTThe rodent brief-access taste aversion (BATA) model is an efficient in vivo screening tool for taste assessment. A new E max (maximum effect attributable to the drug) model was developed and further investigated in comparison to three previously published models for analysing the rodent BATA data; the robustness of all the models was discussed.The rodent BATA data were obtained from a series of experiments conducted with a bitter reference compound, quinine hydrochloride dihydrate (QHD). A new E max model that could be applied to both "lick numbers" and "lick ratios" was built and three published models that used lick ratios were employed for analysing the BATA data. IC 50 , the concentration that inhibits 50% of the maximum lick numbers, quantified the oral aversiveness of QHD. One thousand bootstrap datasets were generated from the original data. All models were applied to estimate the confidence intervals of the IC 50s without symmetric assumption.The IC 50 value obtained from the new E max model was 0.0496 mM (95% CI 0.0297-0.0857) using the lick numbers for analysis, while an IC 50 of 0.0502 mM (95% CI 0.0267-0.0859) was acquired with the lick ratios. Except from one published model, the IC 50 values have a similar range for the 95% CI.The new E max model enabled the analysis of both "lick numbers" and "lick ratios" whereas other models could only handle data presented as "lick ratios". IC 50s obtained with these two types of datasets showed similarity among all models thereby justified the robustness of the new E max model. KEY WORDSBrief-access taste aversion, lickometer, bitterness, E max model, NONMEM

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Pharmacologic Antagonism of the Oral Aversive Taste-Directed Response to Capsaicin in a Mouse Brief Access Taste Aversion Assay

Cited by 13 publications

References 38 publications

A High Throughput In Vivo Assay for Taste Quality and Palatability

A High Throughput In Vivo Assay for Taste Quality and Palatability

Piperine, a dietary phytochemical, inhibits angiogenesis

Development of a model for robust and exploratory analysis of the rodent brief-access taste aversion data

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