, Volume 233, Issue 18, pp 3417–3427 | Cite as

Enhancing effect of menthol on nicotine self-administration in rats

  • Lisa Biswas
  • Erin Harrison
  • Yongzhen Gong
  • Ramachandram Avusula
  • Jonathan Lee
  • Meiyu Zhang
  • Thomas Rousselle
  • Janice Lage
  • Xiu LiuEmail author
Original Investigation



Tobacco smoking is a leading preventable cause of premature death in the USA. Menthol is a significant flavoring additive in tobacco products. Clinical evidence suggests that menthol may promote tobacco smoking and nicotine dependence. However, it is unclear whether menthol enhances the reinforcing actions of nicotine and thus facilitates nicotine consumption. This study employed a rat model of nicotine self-administration to examine the effects of menthol on nicotine-taking behavior.


Male Sprague-Dawley rats were trained in daily 1-h sessions to press a lever for intravenous nicotine self-administration under a fixed-ratio 5 schedule of reinforcement. In separate groups, rats self-administered nicotine at four different doses (0.0075, 0.015, 0.03, and 0.06 mg/kg/infusion). Five minutes prior to the two test sessions, menthol (5 mg/kg) or its vehicle was administered intraperitoneally in all rats in a counterbalanced design within each group. In separate rats that self-administered 0.015 mg/kg/infusion nicotine, menthol dose-response function was determined. Menthol was also tested on food self-administration.


An inverted U-shaped nicotine dose-response curve was observed. Menthol pretreatment shifted the nicotine dose-response curve to the left. The facilitating effect of menthol on the self-administration of 0.015 mg/kg/infusion nicotine was dose-dependent, whereas it produced similar effects at doses above the threshold of 2.5 mg/kg. Menthol tended to suppress the self-administration of food pellets.


These data demonstrate that menthol enhances the reinforcing effects of nicotine, and the effect of menthol was specific to nicotine. The findings suggest that menthol directly facilitates nicotine consumption, thereby contributing to tobacco smoking.


Dose-response Menthol Nicotine Rats Reinforcement Self-administration 



This work was supported by the National Institute on Drug Abuse and Food and Drug Administration Center for Tobacco Products (R01DA037277 to X. Liu). The funding source had no other role other than financial support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.


  1. Abobo CV, Ma J, Liang D (2012) Effect of menthol on nicotine pharmacokinetics in rats after cigarette smoke inhalation. Nicotine Tob Res 14:801–808CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ahijevych K, Parsley LA (1999) Smoke constituent exposure and stage of change in black and white women cigarette smokers. Addict Behav 24:115–120CrossRefPubMedGoogle Scholar
  3. Ai J, Taylor KM, Lisko JG, Tran H, Watson CH, Holman MR (2016) Menthol content in US marketed cigarettes. Nicotine Tob Res 18:1575–1580CrossRefGoogle Scholar
  4. Alberg AJ, Shopland DR, Cummings KM (2014) The 2014 Surgeon General’s report: commemorating the 50th Anniversary of the 1964 Report of the Advisory Committee to the US Surgeon General and updating the evidence on the health consequences of cigarette smoking. Am J Epidemiol 179:403–412CrossRefPubMedPubMedCentralGoogle Scholar
  5. Alsharari SD, King JR, Nordman JC, Muldoon PP, Jackson A, Zhu AZ, Tyndale RF, Kabbani N, Damaj MI (2015) Effects of menthol on nicotine pharmacokinetic, pharmacology and dependence in mice. PLoS One 10:e0137070CrossRefPubMedPubMedCentralGoogle Scholar
  6. Anand R, Lin L (2001) Menthol modulates the functional properties of nicotinic receptors. Soc Neurosci Abstr 137:14Google Scholar
  7. Anderson SJ (2011a) Marketing of menthol cigarettes and consumer perceptions: a review of tobacco industry documents. Tob Control 20(Suppl 2):ii20–ii28PubMedPubMedCentralGoogle Scholar
  8. Anderson SJ (2011b) Menthol cigarettes and smoking cessation behaviour: a review of tobacco industry documents. Tob Control 20(Suppl 2):ii49–ii56PubMedPubMedCentralGoogle Scholar
  9. Andre E, Campi B, Materazzi S, Trevisani M, Amadesi S, Massi D, Creminon C, Vaksman N, Nassini R, Civelli M, Baraldi PG, Poole DP, Bunnett NW, Geppetti P, Patacchini R (2008) Cigarette smoke-induced neurogenic inflammation is mediated by alpha, beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest 118:2574–2582PubMedPubMedCentralGoogle Scholar
  10. Ashoor A, Nordman JC, Veltri D, Yang KH, Al Kury L, Shuba Y, Mahgoub M, Howarth FC, Sadek B, Shehu A, Kabbani N, Oz M (2013) Menthol binding and inhibition of alpha7-nicotinic acetylcholine receptors. PLoS One 8:e67674CrossRefPubMedPubMedCentralGoogle Scholar
  11. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857CrossRefPubMedGoogle Scholar
  12. Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124:1269–1282CrossRefPubMedGoogle Scholar
  13. Benowitz NL, Herrera B, Jacob P 3rd (2004) Mentholated cigarette smoking inhibits nicotine metabolism. J Pharmacol Exp Ther 310:1208–1215CrossRefPubMedGoogle Scholar
  14. Benowitz NL, Perez-Stable EJ, Fong I, Modin G, Herrera B, Jacob P 3rd (1999) Ethnic differences in N-glucuronidation of nicotine and cotinine. J Pharmacol Exp Ther 291:1196–1203PubMedGoogle Scholar
  15. Benowitz NL, Samet JM (2011) The threat of menthol cigarettes to U.S. public health. N Engl J Med 364:2179–2181CrossRefPubMedGoogle Scholar
  16. Best FW (1993) Effects of some cigarette construction parameters on menthol migration and transfer. Rec Adv Tob Sci 19:155–201Google Scholar
  17. Brody AL, Mukhin AG, La Charite J, Ta K, Farahi J, Sugar CA, Mamoun MS, Vellios E, Archie M, Kozman M, Phuong J, Arlorio F, Mandelkern MA (2013) Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers. Int J Neuropsychopharmacol 16:957–966CrossRefPubMedGoogle Scholar
  18. Brunzell DH, McIntosh JM (2012) Alpha 7 nicotinic acetylcholine receptors modulate motivation to self-administer nicotine: implications for smoking and schizophrenia. Neuropsychopharmacology 37:1134–1143CrossRefPubMedGoogle Scholar
  19. Caraballo RS, Asman K (2011) Epidemiology of menthol cigarette use in the United States. Tob Induc Dis 9(Suppl 1):S1CrossRefPubMedPubMedCentralGoogle Scholar
  20. CDC (2014) Current cigarettes moking among adults-United States. Morb. Mortal. Wkly Rep 63:29–34Google Scholar
  21. Celebucki CC, Wayne GF, Connolly GN, Pankow JF, Chang EI (2005) Characterization of measured menthol in 48 U.S. cigarette sub-brands. Nicotine Tob Res 7:523–531CrossRefPubMedGoogle Scholar
  22. Clemens KJ, Lay BP, Holmes NM (2015) Extended nicotine self-administration increases sensitivity to nicotine, motivation to seek nicotine and the reinforcing properties of nicotine-paired cues. Addict Biol. doi: 10.1111/adb.12336
  23. Collins CC, Moolchan ET (2006) Shorter time to first cigarette of the day in menthol adolescent cigarette smokers. Addict Behav 31:1460–1464CrossRefPubMedGoogle Scholar
  24. Curtin GM, Sulsky SI, Van Landingham C, Marano KM, Graves MJ, Ogden MW, Swauger JE (2014) Patterns of menthol cigarette use among current smokers, overall and within demographic strata, based on data from four U.S. government surveys. Regul Toxicol Pharmacol 70:189–196CrossRefPubMedGoogle Scholar
  25. D’Silva J, Boyle RG, Lien R, Rode P, Okuyemi KS (2012) Cessation outcomes among treatment-seeking menthol and nonmenthol smokers. Am J Prev Med 43:S242–S248CrossRefPubMedGoogle Scholar
  26. Daniel JW, Rycroft D (1976) l-menthol: absorption, excretion and biotransformation in rats, mice, Syrian hamsters and guinea pigs. Brown and Williamson. 570312869/2918.Google Scholar
  27. Delnevo CD, Gundersen DA, Hrywna M, Echeverria SE, Steinberg MB (2011) Smoking-cessation prevalence among U.S. smokers of menthol versus non-menthol cigarettes. Am J Prev Med 41:357–365CrossRefPubMedGoogle Scholar
  28. Delnevo CD, Villanti AC, Wackowski OA, Gundersen DA, Giovenco DP (2015) The influence of menthol, e-cigarettes and other tobacco products on young adults’ self-reported changes in past year smoking. Tob Control. doi: 10.1136/tobaccocontrol-2015-052325
  29. Donny EC, Caggiula AR, Knopf S, Brown C (1995) Nicotine self-administration in rats. Psychopharmacology 122:390–394CrossRefPubMedGoogle Scholar
  30. Eccles R (1994) Menthol and related cooling compounds. J Pharm Pharmacol 46:618–630CrossRefPubMedGoogle Scholar
  31. Eccles R (2000) Role of cold receptors and menthol in thirst, the drive to breathe and arousal. Appetite 34:29–35CrossRefPubMedGoogle Scholar
  32. Fagan P, Moolchan ET, Hart A Jr, Rose A, Lawrence D, Shavers VL, Gibson JT (2010) Nicotine dependence and quitting behaviors among menthol and non-menthol smokers with similar consumptive patterns. Addiction 105(Suppl 1):55–74CrossRefPubMedGoogle Scholar
  33. Fagan P, Pohkrel P, Herzog T, Pagano I, Vallone D, Trinidad DR, Sakuma KL, Sterling K, Fryer CS, Moolchan E (2015) Comparisons of three nicotine dependence scales in a multiethnic sample of young adult menthol and non-menthol smokers. Drug Alcohol Depend 149:203–211CrossRefPubMedPubMedCentralGoogle Scholar
  34. Farco JA, Grundmann O (2013) Menthol--pharmacology of an important naturally medicinal “cool”. Mini-Rev Med Chem 13:124–131CrossRefPubMedGoogle Scholar
  35. Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE, McNulty S (2006) Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res 26:159–178CrossRefPubMedGoogle Scholar
  36. Federal Trade Commission (2009) Cigarette report for 2006. Federal Trade Commision, Washington DCGoogle Scholar
  37. Gardiner P, Clark PI (2010) Menthol cigarettes: moving toward a broader definition of harm. Nicotine Tob Res: Off J Soc Res Nicotine Tob 12(Suppl 2):S85–S93CrossRefGoogle Scholar
  38. Gentry C, Stoakley N, Andersson DA, Bevan S (2010) The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity. Mol Pain 6:4CrossRefPubMedPubMedCentralGoogle Scholar
  39. Giovino GA (2010) Patterns of and recent trends in the use of mentholated cigarettes in the United States. US FDA Tobacco Product Scientific Advisory Board, Silver Pring, MDGoogle Scholar
  40. Giovino GA, Sidney S, Gfroerer JC, O’Malley PM, Allen JA, Richter PA, Cummings KM (2004) Epidemiology of menthol cigarette use. Nicotine Tob Res 6(Suppl 1):S67–S81CrossRefPubMedGoogle Scholar
  41. Giovino GA, Villanti AC, Mowery PD, Sevilimedu V, Niaura RS, Vallone DM, Abrams DB (2015) Differential trends in cigarette smoking in the USA: is menthol slowing progress? Tob Control 24:28–37CrossRefPubMedGoogle Scholar
  42. Gordon SM, Brinkman MC, Meng RQ, Anderson GM, Chuang JC, Kroeger RR, Reyes IL, Clark PI (2011) Effect of cigarette menthol content on mainstream smoke emissions. Chem Res Toxicol 24:1744–1753CrossRefPubMedGoogle Scholar
  43. Hall AC, Turcotte CM, Betts BA, Yeung WY, Agyeman AS, Burk LA (2004) Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids. Eur J Pharmacol 506:9–16CrossRefPubMedGoogle Scholar
  44. Hans M, Wilhelm M, Swandulla D (2012) Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation. Chem Senses 37:463–469CrossRefPubMedPubMedCentralGoogle Scholar
  45. Heck JD (2009) Smokers of menthol and nonmenthol cigarettes exhibit similar levels of biomarkers of smoke exposure. Cancer Epidemiol Biomark Prev 18:622–629CrossRefGoogle Scholar
  46. Heck JD (2010) A review and assessment of menthol employed as a cigarette flavoring ingredient. Food Chem Toxicol 48(Suppl 2):S1–38CrossRefPubMedGoogle Scholar
  47. Henningfield JE, Benowitz NL, Ahijevych K, Garrett BE, Connolly GN, Wayne GF (2003) Does menthol enhance the addictiveness of cigarettes? An agenda for research. Nicotine Tob Res 5:9–11CrossRefPubMedGoogle Scholar
  48. Hersey JC, Ng SW, Nonnemaker JM, Mowery P, Thomas KY, Vilsaint MC, Allen JA, Haviland ML (2006) Are menthol cigarettes a starter product for youth? Nicotine Tob Res 8:403–413CrossRefPubMedGoogle Scholar
  49. Hersey JC, Nonnemaker JM, Homsi G (2010) Menthol cigarettes contribute to the appeal and addiction potential of smoking for youth. Nicotine Tob Res 12(Suppl 2):S136–S146CrossRefPubMedGoogle Scholar
  50. Hoffman AC (2011) The health effects of menthol cigarettes as compared to non-menthol cigarettes. Tob Induc Dis 9(Suppl 1):S7CrossRefPubMedPubMedCentralGoogle Scholar
  51. Hoffman AC, Miceli D (2011) Menthol cigarettes and smoking cessation behavior. Tob Induc Dis 9(Suppl 1):S6CrossRefPubMedPubMedCentralGoogle Scholar
  52. Hoffman AC, Simmons D (2011) Menthol cigarette smoking and nicotine dependence. Tob Induc Dis 9(Suppl 1):S5CrossRefPubMedGoogle Scholar
  53. Holford TR, Meza R, Warner KE, Meernik C, Jeon J, Moolgavkar SH, Levy DT (2014) Tobacco control and the reduction in smoking-related premature deaths in the United States, 1964-2012. JAMA 311:164–171CrossRefPubMedPubMedCentralGoogle Scholar
  54. Hopkins TJ, Rupprecht LE, Hayes MR, Blendy JA, Schmidt HD (2012) Galantamine, an Acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, attenuates nicotine taking and seeking in rats. Neuropsychopharmacology 37:2310–2321CrossRefPubMedPubMedCentralGoogle Scholar
  55. Hopp R (1993) Menthol: its origin, chemistry, physiology and toxicological properties. Rec Adv Tob Sci 19:3–46Google Scholar
  56. Hymowitz N, Mouton C, Edkholdt H (1995) Menthol cigarette smoking in African Americans and Whites. Tob Control 4:194–195CrossRefPubMedCentralGoogle Scholar
  57. Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–265CrossRefPubMedGoogle Scholar
  58. Journigan VB, Zaveri NT (2013) TRPM8 ion channel ligands for new therapeutic applications and as probes to study menthol pharmacology. Life Sci 92:425–437CrossRefPubMedGoogle Scholar
  59. Karashima Y, Damann N, Prenen J, Talavera K, Segal A, Voets T, Nilius B (2007) Bimodal action of menthol on the transient receptor potential channel TRPA1. J Neurosci 27:9874–9884CrossRefPubMedGoogle Scholar
  60. Keh SM, Facer P, Yehia A, Sandhu G, Saleh HA, Anand P (2011) The menthol and cold sensation receptor TRPM8 in normal human nasal mucosa and rhinitis. Rhinology 49:453–457PubMedGoogle Scholar
  61. Kramlinger VM, von Weymarn LB, Murphy SE (2012) Inhibition and inactivation of cytochrome P 450 2A6 and cytochrome P450 2A13 by menthofuran, beta-nicotyrine and menthol. Chem Biol Interact 197:87–92CrossRefPubMedPubMedCentralGoogle Scholar
  62. Kreslake JM, Wayne GF, Alpert HR, Koh HK, Connolly GN (2008) Tobacco industry control of menthol in cigarettes and targeting of adolescents and young adults. Am J Public Health 98:1685–1692CrossRefPubMedPubMedCentralGoogle Scholar
  63. Levy DT, Blackman K, Tauras J, Chaloupka FJ, Villanti AC, Niaura RS, Vallone DM, Abrams DB (2011) Quit attempts and quit rates among menthol and nonmenthol smokers in the United States. Am J Public Health 101:1241–1247CrossRefPubMedPubMedCentralGoogle Scholar
  64. Liu B, Fan L, Balakrishna S, Sui A, Morris JB, Jordt SE (2013) TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. Pain 154:2169–2177CrossRefPubMedPubMedCentralGoogle Scholar
  65. Liu BY, Lin YJ, Lee HF, Ho CY, Ruan T, Kou YR (2015) Menthol suppresses laryngeal C-fiber hypersensitivity to cigarette smoke in a rat model of gastroesophageal reflux disease: the role of TRPM8. J Appl Physiol 118:635–645CrossRefPubMedGoogle Scholar
  66. Lugton W, Dyas B, Binns R (1978) Human volunteer smoking studies on mentholated cigarettes. Brown and Williamson.: 750312337/2364.Google Scholar
  67. MacDougall JM, Fandrick K, Zhang X, Serafin SV, Cashman JR (2003) Inhibition of human liver microsomal (S)-nicotine oxidation by (-)-menthol and analogues. Chem Res Toxicol 16:988–993CrossRefPubMedGoogle Scholar
  68. McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52–58CrossRefPubMedGoogle Scholar
  69. Muscat JE, Chen G, Knipe A, Stellman SD, Lazarus P, Richie JP Jr (2009) Effects of menthol on tobacco smoke exposure, nicotine dependence, and NNAL glucuronidation. Cancer Epidemiol Biomark Prev 18:35–41CrossRefGoogle Scholar
  70. Nonnemaker J, Hersey J, Homsi G, Busey A, Allen J, Vallone D (2013) Initiation with menthol cigarettes and youth smoking uptake. Addiction 108:171–178CrossRefPubMedGoogle Scholar
  71. Okuyemi KS, Ahluwalia JS, Ebersole-Robinson M, Catley D, Mayo MS, Resnicow K (2003) Does menthol attenuate the effect of bupropion among African American smokers? Addiction 98:1387–1393CrossRefPubMedGoogle Scholar
  72. Pan R, Tian Y, Gao R, Li H, Zhao X, Barrett JE, Hu H (2012) Central mechanisms of menthol-induced analgesia. J Pharmacol Exp Ther 343:661–672CrossRefPubMedGoogle Scholar
  73. Pearson JL, Abrams DB, Niaura RS, Richardson A, Vallone DM (2012) A ban on menthol cigarettes: impact on public opinion and smokers’ intention to quit. Am J Public Health 102:e107–e114CrossRefPubMedPubMedCentralGoogle Scholar
  74. Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705–715CrossRefPubMedGoogle Scholar
  75. Rabinoff M, Caskey N, Rissling A, Park C (2007) Pharmacological and chemical effects of cigarette additives. Am J Public Health 97:1981–1991CrossRefPubMedPubMedCentralGoogle Scholar
  76. Rath P, Hilton JK, Sisco NJ, Van Horn WD (2015) Implications of human transient receptor potential melastatin 8 (TRPM8) channel gating from menthol binding studies of the sensing domain. Biochemistry 55:0114–0124CrossRefGoogle Scholar
  77. Reid G, Flonta ML (2001) Physiology. Cold current in thermoreceptive neurons. Nature:413–480Google Scholar
  78. Rice ME, Cragg SJ (2004) Nicotine amplifies reward-related dopamine signals in striatum. Nat Neurosci 7:583–584CrossRefPubMedGoogle Scholar
  79. Richter P, Beistle D, Pederson L, O'Hegarty M (2008) Small-group discussions on menthol cigarettes: listening to adult African American smokers in Atlanta, Georgia. Ethn Health 13:171–182CrossRefPubMedGoogle Scholar
  80. SAMHSA (2009) The NSDUH report: use of menthol cigarettes. Substance Abuse and Mental Health Services Administration. Office of Appied Studies, Rockville, MDGoogle Scholar
  81. Smith SS, Fiore MC, Baker TB (2014) Smoking cessation in smokers who smoke menthol and non-menthol cigarettes. Addiction 109:2107–2117CrossRefPubMedPubMedCentralGoogle Scholar
  82. Talavera K, Gees M, Karashima Y, Meseguer VM, Vanoirbeek JA, Damann N, Everaerts W, Benoit M, Janssens A, Vennekens R, Viana F, Nemery B, Nilius B, Voets T (2009) Nicotine activates the chemosensory cation channel TRPA1. Nat Neurosci 12:1293–1299CrossRefPubMedGoogle Scholar
  83. Tani M, Onimaru H, Ikeda K, Kawakami K, Homma I (2010) Menthol inhibits the respiratory rhythm in brainstem preparations of the newborn rats. Neuroreport 21:1095–1099CrossRefPubMedGoogle Scholar
  84. Teichert RW, Memon T, Aman JW, Olivera BM (2014) Using constellation pharmacology to define comprehensively a somatosensory neuronal subclass. Proc Natl Acad Sci U S A 111:2319–2324CrossRefPubMedPubMedCentralGoogle Scholar
  85. Thorup I, Wurtzen G, Carstensen J, Olsen P (1983) Short term toxicity study in rats dosed with pulegone and menthol. Toxicol Lett 19:207–210CrossRefPubMedGoogle Scholar
  86. Tobacco (2011) Tobacco Products Scientific Advisory Committee. Menthol cigarettes and public health: review of the scientific evidence and recommendations. US Food and Drug Administration, Washington DCGoogle Scholar
  87. TPSAC (2011) Menthol cigarettes and public health: review of the scientific evidence and recommendations. Food and Drug Administration, Rockville, MDGoogle Scholar
  88. Umezu T, Morita M (2003) Evidence for the involvement of dopamine in ambulation promoted by menthol in mice. J Pharmacol Sci 91:125–135CrossRefPubMedGoogle Scholar
  89. Wackowski O, Delnevo CD (2007) Menthol cigarettes and indicators of tobacco dependence among adolescents. Addict Behav 32:1964–1969CrossRefPubMedGoogle Scholar
  90. Wang J, Roethig HJ, Appleton S, Werley M, Muhammad-Kah R, Mendes P (2010) The effect of menthol containing cigarettes on adult smokers’ exposure to nicotine and carbon monoxide. Regul Toxicol Pharmacol 57:24–30CrossRefPubMedGoogle Scholar
  91. Wang T, Wang B, Chen H (2014) Menthol facilitates the intravenous self-administration of nicotine in rats. Front Behav Neurosci 8:437PubMedPubMedCentralGoogle Scholar
  92. Warren GW, Alberg AJ, Kraft AS, Cummings KM (2014) The 2014 surgeon General’s report: “The health consequences of smoking–50 years of progress”: a paradigm shift in cancer care. Cancer 120:1914–1916CrossRefPubMedGoogle Scholar
  93. Watkins SS, Epping-Jordan MP, Koob GF, Markou A (1999) Blockade of nicotine self-administration with nicotinic antagonists in rats. Pharmacol Biochem Behav 62:743–751CrossRefPubMedGoogle Scholar
  94. Watson HR, Hems R, Rowsell DG, Spring DJ (1978) New compounds with the menthol cooling effect. J Cosmetic Chem 29:185–200Google Scholar
  95. Wayne G, Connolly GN (2004) Application, function, and effects of menthol in cigarettes: a survey of tobacco industry documents. Nicotine Tob Res 6(suppl 1):S43–S54CrossRefGoogle Scholar
  96. Werley MS, Coggins CR, Lee PN (2007) Possible effects on smokers of cigarette mentholation: a review of the evidence relating to key research questions. Regul Toxicol Pharmacol 47:189–203CrossRefPubMedGoogle Scholar
  97. Williams JM, Gandhi KK, Steinberg ML, Foulds J, Ziedonis DM, Benowitz NL (2007) Higher nicotine and carbon monoxide levels in menthol cigarette smokers with and without schizophrenia. Nicotine Tob Res 9:873–881CrossRefPubMedGoogle Scholar
  98. Xiao B, Dubin AE, Bursulaya B, Viswanath V, Jegla TJ, Patapoutian A (2008) Identification of transmembrane domain 5 as a critical molecular determinant of menthol sensitivity in mammalian TRPA1 channels. J Neurosci 28:9640–9651CrossRefPubMedPubMedCentralGoogle Scholar
  99. Zhang H, Sulzer D (2004) Frequency-dependent modulation of dopamine release by nicotine. Nat Neurosci 7:581–582CrossRefPubMedGoogle Scholar
  100. Zhang XB, Jiang P, Gong N, Hu XL, Fei D, Xiong ZQ, Xu L, Xu TL (2008) A-type GABA receptor as a central target of TRPM8 agonist menthol. PLoS One 3:e3386CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Lisa Biswas
    • 1
  • Erin Harrison
    • 1
  • Yongzhen Gong
    • 1
  • Ramachandram Avusula
    • 1
  • Jonathan Lee
    • 1
  • Meiyu Zhang
    • 1
  • Thomas Rousselle
    • 1
  • Janice Lage
    • 1
  • Xiu Liu
    • 1
    Email author
  1. 1.Department of PathologyUniversity of Mississippi Medical CenterJacksonUSA

Personalised recommendations