Abstract
Ethanol is a known oral trigeminal stimulant and recent data indicate that these effects are mediated in part by transient receptor potential channel vanilloid receptor 1 (TRPV1). The importance of this receptor in orally mediated ethanol avoidance is presently unknown. Here, we compared orosensory responding to ethanol in TRPV1-deficient and wild type mice in a brief-access paradigm that assesses orosensory influences by measuring immediate licking responses to small stimulus volumes. TRPV1−/− and control mice were tested with six concentrations of ethanol (3, 5, 10, 15, 25, 40%), capsaicin (0.003, 0.01, 0.03, 0.1, 0.3, 1 mM), sucrose (0.003, 0.01, 0.03, 0.1, 0.3, 1 M), and quinine (0.01, 0.03, 0.1, 0.3, 1, 3 mM) and psychophysical concentration-response functions were generated for each genotype and stimulus. TRPV1 knockouts displayed reduced oral avoidance responses to ethanol regardless of concentration, insensitivity to capsaicin, and little to no difference in sweet or bitter taste responding relative to wild type mice. These data indicate that the TRPV1 channel plays a role in orosensory-mediated ethanol avoidance, but that other receptor mechanisms likely also contribute to aversive oral responses to alcohol.
References
Arvidsson J, Gobel S (1981) An HRP study of the central projections of primary trigeminal neurons which innervate tooth pulps in the cat. Brain Res 210:1–16. doi:10.1016/0006-8993(81)90880-5
Bachmanov AA, Tordoff MG, Beauchamp GK (1996) Ethanol consumption and taste preferences in C57BL/6ByJ and 129/J mice. Alcohol Clin Exp Res 20:201–206. doi:10.1111/j.1530-0277.1996.tb01630.x
Bachmanov AA, Reed DR, Li X, Li S, Beauchamp GK, Tordoff MG (2002) Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ × 129P3/J F2 intercross. Genome Res 12:1257–1268. doi:10.1101/gr.129702
Blednov YA, Harris RA (2007) Deletion of vanilloid receptor (TRPV1) increases ethanol consumption: possible role of endocannabinoids. Alcohol Clin Exp Res 31(suppl):9A. doi:10.1111/j.1530-0277.2007.00412.x
Blednov YA, Walker D, Martinez M, Levine M, Damak S, Margolskee RF (2008) Perception of sweet taste is important for voluntary alcohol consumption in mice. Genes Brain Behav 7:1–13
Blizard DA (2007) Sweet and bitter taste of ethanol in C57BL/6J and DBA2/J mouse strains. Behav Genet 37:146–159. doi:10.1007/s10519-006-9121-4
Bolivar VJ, Cook MN, Flaherty L (2001) Mapping of quantitative trait loci with knockout/congenic strains. Genome Res 11:1549–1552. doi:10.1101/gr.194001
Boughter JD, St John SJ, Noel DT, Ndubuizu O, Smith DV (2002) A brief-access test for bitter taste in mice. Chem Senses 27:133–142. doi:10.1093/chemse/27.2.133
Boughter JD, Raghow S, Nelson TM, Munger SD (2005) Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli. BMC Genet 6:36. doi:10.1186/1471-2156-6-36
Brasser SM, Mozhui K, Smith DV (2005) Differential covariation in taste responsiveness to bitter stimuli in rats. Chem Senses 30:793–799. doi:10.1093/chemse/bji071
Brasser SM, Norman MB, Lemon CH, Hamre KM, Margolskee RF, Smith DV (2006) T1r3 sweet taste receptor deficient mice show an absence of preference for ethanol. Soc Neurosci Abstr 194.7
Carstens E, Kuenzler N, Handwerker HO (1998) Activation of neurons in rat trigeminal subnucleus caudalis by different irritant chemicals applied to oral or ocular mucosa. J Neurophysiol 80:465–492
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824. doi:10.1038/39807
Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313. doi:10.1126/science.288.5464.306
Crusio WE (2004) Flanking gene and genetic background problems in genetically manipulated mice. Biol Psychiatry 56:381–385. doi:10.1016/j.biopsych.2003.12.026
Danilova V, Hellekant G (2002) Oral sensation of ethanol in a primate model III: responses in the lingual branch of the trigeminal nerve of Macaca mulatta. Alcohol 26:3–16. doi:10.1016/S0741-8329(01)00178-1
Davis JD (1973) The effectiveness of some sugars in stimulating licking behavior in the rat. Physiol Behav 11:39–45. doi:10.1016/0031-9384(73)90120-0
Di Lorenzo PM, Kiefer SW, Rice AG, Garcia J (1986) Neural and behavioral responsivity to ethyl alcohol as a tastant. Alcohol 3:55–61. doi:10.1016/0741-8329(86)90071-6
Diamant H, Funakoshi M, Strom L, Zotterman Y (1963) Electrophysiological studies on human taste nerves. In: Zotterman Y (ed) Olfaction and taste I. Pergamon, New York, pp 193–203
Dotson CD, Spector AC (2004) The relative affective potency of glycine, L-serine and sucrose as assessed by a brief-access taste test in inbred strains of mice. Chem Senses 29:489–498. doi:10.1093/chemse/bjh051
Dotson CD, Spector AC (2005) Drinking spout orifice size affects licking behavior in inbred mice. Physiol Behav 85:655–661. doi:10.1016/j.physbeh.2005.06.010
Gilmore MM, Green BG (1993) Sensory irritation and taste produced by NaCl and citric acid: effects of capsaicin desensitization. Chem Senses 18:257–272. doi:10.1093/chemse/18.3.257
Glendinning JI, Gresack J, Spector AC (2002) A high-throughput screening procedure for identifying mice with aberrant taste and oromotor function. Chem Senses 27:461–474. doi:10.1093/chemse/27.5.461
Glendinning JI, Bloom LD, Onishi M, Zheng KH, Damak S, Margolskee RF, Spector AC (2005) Contribution of α-gustducin to taste-guided licking responses of mice. Chem Senses 30:299–316. doi:10.1093/chemse/bji025
Green BG (1987) The sensitivity of the tongue to ethanol. Ann NY Acad Sci 510:315–317. doi:10.1111/j.1749-6632.1987.tb43541.x
Green BG (1988) Spatial and temporal factors in the perception of ethanol irritation on the tongue. Percept Psychophys 44:108–116
Green BG (1990) Effects of thermal, mechanical, and chemical stimulation on the perception of oral irritation. In: Green BG, Mason JR, Kare MR (eds) Chemical senses, vol 2, irritation. Marcel Dekker, New York, pp 171–175
Green BG, Gelhard B (1989) Salt as an oral irritant. Chem Senses 14:259–271. doi:10.1093/chemse/14.2.259
Hellekant G (1965) The effect of ethyl alcohol on non-gustatory receptors of the tongue of the cat. Acta Physiol Scand 65:243–250
Hellekant G, Danilova V, Roberts T, Ninomiya Y (1997) The taste of ethanol in a primate model: I. Chorda tympani nerve response in Macaca mulatta. Alcohol 14:473–484. doi:10.1016/S0741-8329(96)00215-7
Ishida Y, Ugawa S, Ueda T, Murakami S, Shimada S (2002) Vanilloid receptor subtype-1 (VR1) is specifically localized to taste papillae. Brain Res Mol Brain Res 107:17–22. doi:10.1016/S0169-328X(02)00441-2
Jacquin MF, Semba K, Egger MD, Rhoades RW (1983) Organization of HRP-labeled trigeminal mandibular primary afferent neurons in the rat. J Comp Neurol 215:397–420. doi:10.1002/cne.902150405
Kido MA, Muroya H, Yamaza T, Terada Y, Tanaka T (2003) Vanilloid receptor expression in the rat tongue and palate. J Dent Res 82:393–397
Kiefer SW, Lawrence GJ (1988) The sweet-bitter taste of alcohol: aversion generalization to various sweet-quinine mixtures in the rat. Chem Senses 13:633–641. doi:10.1093/chemse/13.4.633
Kiefer SW, Mahadevan RS (1993) The taste of alcohol for rats as revealed by aversion generalization tests. Chem Senses 18:509–522. doi:10.1093/chemse/18.5.509
Kiefer SW, Morrow NS (1991) Odor cue mediation of alcohol aversion learning in rats lacking gustatory neocortex. Behav Neurosci 105:25–32. doi:10.1037/0735-7044.105.1.25
Kiefer SW, Bice PJ, Orr MR, Dopp JM (1990) Similarity of taste reactivity responses to alcohol and sucrose mixtures in rats. Alcohol 7:115–120. doi:10.1016/0741-8329(90)90071-J
Lemon CH, Brasser SM, Smith DV (2004) Alcohol activates a sucrose-responsive gustatory neural pathway. J Neurophysiol 92:536–544. doi:10.1152/jn.00097.2004
Liu L, Simon SA (1998) Responses of cultured rat trigeminal ganglion neurons to bitter tastants. Chem Senses 23:125–130
Marfurt CF (1981) The central projections of trigeminal primary afferent neurons in the cat as determined by the tranganglionic transport of horseradish peroxidase. J Comp Neurol 203:785–798. doi:10.1002/cne.902030414
Mattes RD, DiMeglio D (2001) Ethanol perception and ingestion. Physiol Behav 72:217–229. doi:10.1016/S0031-9384(00)00397-8
Mistretta CA (1971) Permeability of tongue epithelium and its relation to taste. Am J Physiol 220:1162–1167
Okuni Y (1977) Response of chorda tympani fibers of the rat to pungent spices and irritants in pungent spices. Shikwa Gakuho 77:1323–1349
Ruiz C, Gutknecht S, Delay E, Kinnamon S (2006) Detection of NaCl and KCl in TRPV1 knockout mice. Chem Senses 31:813–820. doi:10.1093/chemse/bjl024
Scinska A, Koros E, Habrat B, Kukwa A, Kostowski W, Bienkowski P (2000) Bitter and sweet components of ethanol taste in humans. Drug Alcohol Depend 60:199–206. doi:10.1016/S0376-8716(99)00149-0
Simon SA, Sostman AL (1991) Electrophysiological responses to non-electrolytes in lingual nerve of rat and in lingual epithelia of dog. Arch Oral Biol 36:805–813. doi:10.1016/0003-9969(91)90030-X
Simons CT, Boucher Y, Carstens MI, Carstens E (2003) Lack of quinine-evoked activity in rat trigeminal subnucleus caudalis. Chem Senses 28:253–259. doi:10.1093/chemse/28.3.253
Smith JC (2001) The history of the ‘Davis Rig’. Appetite 36:93–98. doi:10.1006/appe.2000.0372
Smith JC, Davis JD O, Keefe GB (1992) Lack of an order effect in brief contact taste tests with closely spaced test trials. Physiol Behav 52:1107–1111. doi:10.1016/0031-9384(92)90467-G
Spector AC, Redman R, Garcea M (1996) The consequences of gustatory nerve transection on taste-guided licking of sucrose and maltose in the rat. Behav Neurosci 110:1096–1109. doi:10.1037/0735-7044.110.5.1096
St John SJ, Garcea M, Spector AC (1994) Combined, but not single, gustatory nerve transection substantially alters taste-guided licking behavior to quinine in rats. Behav Neurosci 108:131–140. doi:10.1037/0735-7044.108.1.131
Sudo S, Sudo M, Simons CT, Dessirier JM, Carstens E (2002) Sensitization of trigeminal caudalis neuronal responses to intraoral acid and salt stimuli and desensitization by nicotine. Pain 98:277–286. doi:10.1016/S0304-3959(02)00025-8
Szallasi A, Cortright DN, Blum CA, Eid SR (2007) The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov 6:357–372. doi:10.1038/nrd2280
Takemura M, Sugimoto T, Shigenaga Y (1991) Difference in central projection of primary afferents innervating facial and intraoral structures in the rat. Exp Neurol 111:324–331. doi:10.1016/0014-4886(91)90099-X
Trevisani M, Smart D, Gunthorpe MJ, Tognetto M, Barbieri M, Campi B, Amadesi S, Gray J, Jerman JC, Brough SJ, Owen D, Smith GD, Randall AD, Harrison S, Bianchi A, Davis JB, Geppetti P (2002) Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1. Nat Neurosci 5:546–551. doi:10.1038/nn0602-852
Trevisani M, Gazzieri D, Benvenuti F, Campi B, Dinh QT, Groneberg DA, Rigoni M, Emonds Alt X, Creminon C, Fischer A, Geppetti P, Harrison S (2004) Ethanol causes inflammation in the airways by a neurogenic and TRPV1-dependent mechanism. J Pharmacol Exp Ther 309:1167–1173. doi:10.1124/jpet.103.064162
Wilson CW, Brien O, Mac C, Airt JG (1973) The effect of metronidazole on the human taste threshold to alcohol. Br J Addict Alcohol Other Drugs 68:99–110
Zanotto KL, Merrill AW, Carstens MI, Carstens E (2007) Neurons in superficial trigeminal subnucleus caudalis responsive to oral cooling, menthol, and other irritant stimuli. J Neurophysiol 97:966–978. doi:10.1152/jn.00996.2006
Acknowledgments
This research was supported by NIH Grant AA015741. We thank Robert Robinson and Sara Kazemi for assistance with data collection. A portion of these data were presented at the 2007 meeting of the Society for Neuroscience, San Diego, CA.
Author information
Authors and Affiliations
Corresponding author
Additional information
Edited by Tamara Phillips.
Rights and permissions
About this article
Cite this article
Ellingson, J.M., Silbaugh, B.C. & Brasser, S.M. Reduced Oral Ethanol Avoidance in Mice Lacking Transient Receptor Potential Channel Vanilloid Receptor 1. Behav Genet 39, 62–72 (2009). https://doi.org/10.1007/s10519-008-9232-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10519-008-9232-1