Quantitative assessment of TRPM5-dependent oral aversiveness of pharmaceuticals using a mouse brief-access taste aversion assay

Behav Pharmacol. 2008 Oct;19(7):673-82. doi: 10.1097/FBP.0b013e3283123cd6.


Many orally administered pharmaceuticals are regarded by humans as aversive, most often described as 'bitter'. Taste aversiveness often leads to patient noncompliance and reduced treatment effectiveness. 'Bitter' taste is mediated by T2R G-protein coupled receptors through a peripheral signaling pathway critically dependent upon function of the TRPM5 ion channel. The brief-access taste aversion (BATA) assay operationally defines aversive taste as suppression of the rate at which a rodent licks from sipper tubes that deliver tastant solutions or suspensions. We have used a mouse BATA assay for rapid quantification of oral aversiveness from a set of 20 active pharmaceutical ingredients (APIs). Robust lick-rate dose-response functions were obtained from both C57BL/6J wild type (WT) and C57BL/6J/TRPM5-/- (TRPM5 knockout) mouse strains, generating reliable determinations of potency and relative maximal oral aversiveness for each API. A subset of APIs was also evaluated in a human bitterness assessment test; effective concentrations for half-maximum responses (EC50s) from both the human test and WT mouse BATA were equivalent. Relative to WT potencies, EC50s from TRPM5 knockout mice were right-shifted more than 10-fold for most APIs. However, APIs were identified for which EC50s were essentially identical in both mouse strains, indicating a TRPM5-independent alternative aversive pathway. Our results suggest the BATA assay will facilitate formulation strategies and taste assessment of late development-phase APIs.

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drinking Behavior / physiology
  • Female
  • Gene Expression / physiology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nonprescription Drugs*
  • Prescription Drugs*
  • Species Specificity
  • TRPM Cation Channels / genetics*
  • Taste / genetics*
  • Taste Threshold / genetics


  • Nonprescription Drugs
  • Prescription Drugs
  • TRPM Cation Channels
  • TRPM5 protein, human