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Discriminative Stimulus Properties of S(−)-Nicotine: “A Drug for All Seasons”

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The Behavioral Neuroscience of Drug Discrimination

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 39))

Abstract

S(−)-Nicotine is the major pharmacologically active substance in tobacco and can function as an effective discriminative stimulus in both experimental animals and humans. In this model, subjects must detect and communicate the nicotine drug state versus the non-drug state. This review describes the usefulness of the procedure to study nicotine, presents a general overview of the model, and provides some relevant methodological details for the establishment of this drug as a stimulus. Once established, the (−)-nicotine stimulus can be characterized for dose response and time course effects. Moreover, tests can be conducted to determine the similarity of effects produced by test drugs to those produced by the training dose of nicotine. Such tests have shown that the stimulus effects of nicotine are stereoselective [S(−)-nicotine >R(+)-nicotine] and that other “natural” tobacco alkaloids and (−)-nicotine metabolites can produce (−)-nicotine-like effects, but these drugs are much less potent than (−)-nicotine. Stimulus antagonism tests with mecamylamine and DHβE (dihydro-β-erythroidine) indicate that the (−)-nicotine stimulus is mediated via α4β2 nicotinic acetylcholine receptors (nAChRs) in brain; dopamine systems also are likely involved. Individuals who try to cease their use of nicotine-based products are often unsuccessful. Bupropion (Zyban®) and varenicline (Chantix®) may be somewhat effective as anti-smoking medications because they probably produce stimulus effects that serve as suitable substitutes for (−)-nicotine in the individual who is motivated to quit smoking. Finally, it is proposed that future drug discrimination studies should apply the model to the issue of maintenance of abstinence from (−)-nicotine-based products.

Sadly, Dr. John A. Rosecrans passed away during the writing of this chapter. John inspired both students and colleagues with his keen interest and enthusiasm in matters related to biomedical research and, especially, nicotine. Most of all, John will be remembered and missed for his friendship. The editors (J. H. Porter and A. J. Prus) of the book (The Behavioural Neuroscience of Drug Discrimination) this chapter is published in would also like to note that the book is dedicated to Dr. John A. Rosecrans.

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References

  1. Efron DH (1967) Ethnopharmacologic search for psychoactive drugs. In: Proceedings of a symposium held in San Francisco, CA, 28–30 Jan 1967. Public Health Service Publication Number 1645. U.S. Department of Health, Education and Welfare, Washington, DC

    Google Scholar 

  2. Larson PS, Haagard HB, Silvette H (1961) Tobacco. Experimental and clinical studies: a comprehensive account of the world literature. Williams & Wilkins, Baltimore

    Google Scholar 

  3. Brecher EM (1972) Licit and illicit drugs. Little, Brown, Boston

    Google Scholar 

  4. Leete E, Mueller ME (1982) Biomimetic synthesis of anatabine from 2,5-dihydropyridine produced by the oxidative decarboxylation of baikiain. J Am Chem Soc 104:6440–6444

    CAS  Google Scholar 

  5. Leete E, Slattery SA (1976) Incorporation of [2-14C]-and [6-14C]nicotinic acid into the tobacco alkaloids. Biosynthesis of anatabine and α,β-dipyridyl. J Am Chem Soc 98:6326–6330

    CAS  Google Scholar 

  6. Pinner A (1895) Über Nicotine. Des Konstitutions des Alkaloids. Ber Dtsch Chem Ges 28:456

    CAS  Google Scholar 

  7. Pictet A, Crepieux P (1895) Über Phenyl- and Pyrrylpyrroles and die constitution des nicotines. Ber Dtsch Chem Ges 28:1904

    CAS  Google Scholar 

  8. Spath E, Bretschneider H (1928) Eine neue synthese des Nicotines. Ber Dtsch Chem Ges 61:327

    Google Scholar 

  9. Hudson CS, Neuberger A (1950) The stereochemical formulas of hydroxypyrolines and some related substances. J Org Chem 15:24

    CAS  Google Scholar 

  10. Griffiths RR, Henningfield JE, Bigelow GE (1982) Human cigarette smoking: manipulation of number of puffs per bout, interbout interval and nicotine dose. J Pharmacol Exp Ther 220:256–265

    CAS  Google Scholar 

  11. Matta SG, Balfour DJ, Benowitz NL, Boyd RT, Buccafusco JJ, Caggiula AR, Craig CR, Collins AC, Damaj MI, Donny EC, Gardiner PS, Grady SR, Heberlein U, Leonard SS, Levin ED, Lukas RJ, Markou A, Marks MJ, McCallum SE, Parameswaran N, Perkins KA, Picciotto MR, Quik M, Rose JE, Rothenfluh A, Schafer WR, Stolerman IP, Tyndale RF, Wehner JM, Zirger JM (2007) Guidelines on nicotine dose selection for in vivo research. Psychopharmacology 190:269–319

    CAS  Google Scholar 

  12. Marubio LM, del Mar Arroyo-Jimenez M, Cordero-Erausquin M, Léna C, Le Novère N, de Kerchove, d’Exaerde A, Huchet M, Damaj MI, Changeux JP (1999) Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature 398:805–810

    CAS  Google Scholar 

  13. Lukas RJ, Changeux JP, Le Novère N, Albuquerque EX, Bslfour DJ, Berg DK, Bertrand D, Chiappinelli VA, Clarke PB, Collins AC, Dani JA, Grady SR, Kellar KJ, Lindstrom JM, Marks MJ, Quik M, Taylor PW, Wonnacott S (1999) International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits. Pharmacol Rev 51:397–401

    CAS  Google Scholar 

  14. Corrigall WA, Coen KM, Adamson KL (1994) Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res 653:278–284

    CAS  Google Scholar 

  15. Reavill C, Stolerman IP (1987) Interaction of nicotine with dopaminergic mechanisms assessed through drug discrimination and rotational behaviour in rats. J Psychopharmacol 1:264–273

    CAS  Google Scholar 

  16. Domino EF (2002) Conflicting evidence for the dopamine release theory of nicotine/tobacco dependence. Nihon Shinkei Seishin Yakurigaku Zasshi 22:181–184

    Google Scholar 

  17. Morrison CF, Lee PN (1968) A comparison of the effects of nicotine and physostigmine on a measure of activity in the rat. Psychopharmacologia 13:210–221

    CAS  Google Scholar 

  18. Pradhan SN (1970) Effects of nicotine on several schedules of behavior in rats. Arch Int Pharmacodyn Ther 183:127–138

    CAS  Google Scholar 

  19. Philibin SD, Vann RE, Varvel SA, Covington 3rd HE, Rosecrans JA, James JR, Robinson SE (2005) Differential behavioral responses to nicotine in Lewis and Fischer-344 rats. Pharmacol Biochem Behav 80:87–92

    CAS  Google Scholar 

  20. Prus AJ, Vann RE, Rosecrans JA, James JR, Pehrson AL, O’Connell MM, Philibin SD, Robinson SE (2008) Acute nicotine reduces and repeated nicotine increases spontaneous activity in male and female Lewis rats. Pharmacol Biochem Behav 91:150–154

    CAS  Google Scholar 

  21. Rosecrans JA, Schechter MD (1972) Brain area nicotine levels in male and female rats of two strains. Arch Int Pharmacodyn Ther 196:46–54

    CAS  Google Scholar 

  22. Rosecrans JA (1971) Effects of nicotine on behavioral arousal and brain 5-hydroxytryptamine function in female rats selected for differences in activity. Eur J Pharmacol 14:29–37

    CAS  Google Scholar 

  23. Hendry JS, Rosecrans JA (1982) Effects of nicotine on conditioned and unconditioned behaviors in experimental animals. Pharmacol Ther 17:431–454

    CAS  Google Scholar 

  24. Johnston LM (1942) Tobacco smoking and nicotine. Lancet 2:742

    Google Scholar 

  25. Volle RL, Koelle RB (1975) Ganglionic stimulating and blocking agents. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics, 5th edn. Macmillan, New York, pp. 565–574

    Google Scholar 

  26. Jarvik ME (1979) Tolerance to the effects of tobacco. NIDA Res Monogr 23:150–157

    Google Scholar 

  27. Danielson K, Truman P, Kivell BM (2011) The effects of nicotine and cigarette smoke on the monoamine transporters. Synapse 65:866–879

    CAS  Google Scholar 

  28. James JR, Villanueva HF, Johnson JH, Arezo S, Rosecrans JA (1994) Evidence that nicotine can acutely desensitize central nicotinic acetylcholinergic receptors. Psychopharmacology 114:456–462

    CAS  Google Scholar 

  29. Sershen H, Toth E, Lajha A, Vizi ES (1995) Nicotine effects on presynaptic receptor interactions. Ann N Y Acad Sci 757:238–244

    CAS  Google Scholar 

  30. Rosecrans JA (1989) Nicotine as a discriminative stimulus: a neurobiobehavioral approach to studying central cholinergic mechanisms. J Subst Abus 1:287–300

    Google Scholar 

  31. Altman JL, Albert J, Milstein SL, Greenberg I (1976) Drugs as discriminative events in humans. Psychopharmacol Commun 2:327–330

    CAS  Google Scholar 

  32. Kallman WM, Kallman MJ, Harry GJ, Woodson PP, Rosecrans JA (1978) Nicotine as a discriminative stimulus in human subjects. In: Colpaert FC, Slangen JL (eds) Drug discrimination: applications in CNS pharmacology. Elsevier Biomedical Press, Amsterdam, pp. 211–218

    Google Scholar 

  33. Perkins KA (2011) Nicotine discrimination in humans. In: Glennon RA, Young R (eds) Drug discrimination: application to medicinal chemistry and drug studies. Wiley, New York, pp. 463–481. Chapter 15

    Google Scholar 

  34. Glennon RA, Young R (2011) Drug discrimination: practical considerations. In: Glennon RA, Young R (eds) Drug Discrimination: Application to medicinal chemistry and drug studies. Wiley, New York, pp. 41–128

    Google Scholar 

  35. Morrison CF, Stephenson JA (1969) Nicotine injections as the conditioned stimulus in discrimination learning. Psychopharmacologia 15:351–360

    CAS  Google Scholar 

  36. Schechter MD, Rosecrans JA (1971) C.N.S. effect of nicotine as the discriminative stimulus for the rat in a T-maze. Life Sci 10:821–832

    CAS  Google Scholar 

  37. Schechter MD, Rosecrans JA (1971) Behavioral evidence for two types of cholinergic receptors in the C.N.S. Eur J Pharmacol 15:375–378

    CAS  Google Scholar 

  38. Schechter MD, Rosecrans JA (1972) Effect of mecamylamine on discrimination between nicotine- and arecoline-produced cues. Eur J Pharmacol 17:179–182

    CAS  Google Scholar 

  39. Schechter MD, Rosecrans JA (1972) Nicotine as a discriminative stimulus in rats depleted of norepinephrine or 5-hydroxytryptamine. Psychopharmacologia 24:417–429

    CAS  Google Scholar 

  40. Schechter MD, Rosecrans JA (1972) Nicotine as a discriminative cue in rats: inability of related drugs to produce a nicotine-like cueing effect. Psychopharmacologia 27:379–387

    CAS  Google Scholar 

  41. Schechter MD, Rosecrans JA (1973) D-amphetamine as a discriminative cue: drugs with similar stimulus properties. Eur J Pharmacol 21:212–216

    CAS  Google Scholar 

  42. Perkins KA, Sanders M, Fonte C, Wilson AS, White W, Stiller R, McNamara D (1999) Effects of central and peripheral nicotinic blockade on human nicotine discrimination. Psychopharmacology 142:158–164

    CAS  Google Scholar 

  43. Stolerman IP, Naylor C, Elmer GI, Goldberg SR (1999) Discrimination and self-administration of nicotine by inbred strains of mice. Psychopharmacology 141:297–306

    CAS  Google Scholar 

  44. Takada K, Swedberg MD, Goldberg SR, Katz JL (1989) Discriminative stimulus effects of intravenous l-nicotine and nicotine analogs or metabolites in squirrel monkeys. Psychopharmacology 99:208–212

    CAS  Google Scholar 

  45. Varvel SA, James JR, Bowen S, Rosecrans JA, Karan LD (1999) Discriminative stimulus (DS) properties of nicotine in the C57BL/6 mouse. Pharmacol Biochem Behav 63:27–32

    CAS  Google Scholar 

  46. Kamien JB, Bickel WK, Hughes JR, Higgins ST, Smith BJ (1993) Drug discrimination by humans compared to nonhumans: current status and future directions. Psychopharmacology 111:259–270

    CAS  Google Scholar 

  47. Rosecrans JA (1987) Noncholinergic mechanisms involved in the behavioral and stimulus effects of nicotine, and relationships to the process of nicotine dependence. In: Martin WR, Van Loon GR, Iwamoto ET, Davis L (eds) Tobacco smoking and nicotine: a neurobiological approach. Plenum, New York, pp. 125–139

    Google Scholar 

  48. Rosecrans JA, Chance WT (1977) Cholinergic and non-cholinergic aspects of the discriminative stimulus properties of nicotine. In: Lal H (ed) Discriminative stimulus properties of drugs. Plenum Press, New York, pp. 155–185

    Google Scholar 

  49. Extance K, Goudie AJ (1981) Inter-animal olfactory cues in operant drug discrimination procedures in rats. Psychopharmacology 73:363–371

    CAS  Google Scholar 

  50. Pratt JA, Stolerman IP, Garcha HS, Giardini V, Feyerabend C (1983) Discriminative stimulus properties of nicotine: further evidence for mediation at a cholinergic receptor. Psychopharmacology 81:54–60

    CAS  Google Scholar 

  51. White FJ, Appel JB (1981) A neuropharmacological analysis of the discriminative stimulus properties of fenfluramine. Psychopharmacology 73:110–115

    CAS  Google Scholar 

  52. Chance WT, Murfin D, Krynock GM, Rosecrans JA (1977) A description of the nicotine stimulus and tests of its generalization to amphetamine. Psychopharmacology 55:19–26

    CAS  Google Scholar 

  53. Hirschhorn ID, Rosecrans JA (1974) Studies on the time course and the effect of cholinergic and adrenergic receptor blockers on the stimulus effect of nicotine. Psychopharmacologia 40:109–120

    CAS  Google Scholar 

  54. Stolerman IP, Garcha HS (1989) Temporal factors in drug discrimination: experiments with nicotine. J Psychopharmacol 3:88–97

    CAS  Google Scholar 

  55. Stolerman IP, Garcha HS, Pratt JA, Kumar R (1984) Role of training dose in discrimination of nicotine and related compounds by rats. Psychopharmacology 84:413–419

    CAS  Google Scholar 

  56. Aceto MD, Tucker SM, Ferguson GS, Hinson JR (1986) Rapid and brief tolerance to (+)- and (−)-nicotine in unanesthetized rats. Eur J Pharmacol 132:213–218

    CAS  Google Scholar 

  57. Hicks CS, Sinclair DA (1947) Toxicities of the optical isomers of nicotine and nornicotine. Aust J Exp Biol Med Sci 25:83–86

    CAS  Google Scholar 

  58. Aceto MD, Martin BR, Uwaydah IM, May EL, Harris LS, Izazola-Conde C, Dewey WL, Bradshaw TJ, Vinck WC (1979) Optically pure (+)-nicotine from (+/−)-nicotine and biological comparisons with (−)-nicotine. J Med Chem 22:174–177

    CAS  Google Scholar 

  59. Macht DI (1929) Pharmacological synergism of stereoisomers. Proc Natl Acad Sci 15:63–70

    CAS  Google Scholar 

  60. Macht DI, Davis ME (1934) Toxicity of alpha- and beta-nicotines and nornicotines, an inquiry into chemopharmacodynamic relationships. J Pharmacol Exp Ther 50:93–99

    CAS  Google Scholar 

  61. RTECS (1986) Registry of toxic effects of chemical substances. NIOSH 3A:3060–3424

    Google Scholar 

  62. Domino EF (1965) Some comparative pharmacological actions of (−)-nicotine, its optical isomer, and related compounds. In: von Euler US (ed) Tobacco alkaloids and related compounds, Wenner-Gren center international symposium series, vol 4. Pergamon, New York, London, pp. 303–314

    Google Scholar 

  63. Meltzer LT, Rosecrans JA, Aceto MD, Harris LS (1980) Discriminative stimulus properties of the optical isomers of nicotine. Psychopharmacology 68:283–286

    CAS  Google Scholar 

  64. Romano C, Goldstein A, Jewell NP (1981) Characterization of the receptor mediating the nicotine discriminative stimulus. Psychopharmacology 74:310–315

    CAS  Google Scholar 

  65. Goldberg SR, Risner ME, Stolerman IP, Reavill C, Garcha HS (1989) Nicotine and some related compounds: effects on schedule-controlled behaviour and discriminative properties in rats. Psychopharmacology 97:295–302

    CAS  Google Scholar 

  66. Brioni JD, Kim DJ, O’Neill AB (1996) Nicotine cue: lack of effect of the alpha 7 nicotinic receptor antagonist methyllycaconitine. Eur J Pharmacol 301:1–5

    CAS  Google Scholar 

  67. Hoffmann D, Hoffmann I (1998) Tobacco smoke components. Beiträge zur Tabakforsch ung International 18:49–52

    Google Scholar 

  68. Rodgman A, Perfetti TA (2009) The chemical components of tobacco and tobacco smoke. CRC Press, Taylor & Francis, Boca Raton

    Google Scholar 

  69. Dwoskin LP, Teng L, Buxton ST, Ravard A, Deo N, Crooks PA (1995) Minor alkaloids of tobacco release [3H]dopamine from superfused rat striatal slices. Eur J Pharmacol 276:195–199

    CAS  Google Scholar 

  70. Lőfroth G (1989) Environmental tobacco smoke: overview of chemical composition and genotoxic components. Mutat Res 45:133–144

    Google Scholar 

  71. Felpin F-X, Girard S, Vo-Thanh G, Robins RJ, Villiéras J, Lebreton J (2001) Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco. J Org Chem 66:6305–6312

    CAS  Google Scholar 

  72. Armstrong DW, Wang X, Lee J-T, Liu Y-S (1999) Enantiomeric composition of nornicotine, anatabine, and anabasine in tobacco. Chirality 11:82–84

    CAS  Google Scholar 

  73. Benowitz NL, Hukkanen J, Jacob III P (2009) Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol 192:29–60

    CAS  Google Scholar 

  74. Armstrong DW, Wang X, Ercal N (1998) Enantiomeric composition of nicotine in smokeless tobacco, medicinal products, and commercial reagents. Chirality 10:587–591

    CAS  Google Scholar 

  75. Jacob III P, Yu L, Shulgin AT, Benowitz NL (1999) Minor tobacco alkaloids as biomarkers for tobacco use: comparison of users of cigarettes, smokeless tobacco, cigars, and pipes. Am J Public Health 89:731–736

    Google Scholar 

  76. Leete E (1965) Biosynthesis of alkaloids. Science 147:1000–1006

    CAS  Google Scholar 

  77. Pool WF, Godin CS, Crooks PA (1985) Nicotine racemization during nicotine smoking. Toxicologist 5:232

    Google Scholar 

  78. Armitage AK, Dollery CT, George CF, Houseman TH, Lewis PJ, Turner DM (1975) Absorption and metabolism of nicotine from cigarettes. Br Med J 4:313–316

    CAS  Google Scholar 

  79. Turner DM, Armitage AK, Briant RH, Dollery CT (1975) Metabolism of nicotine by the isolated perfused dog lung. Xenobiotica 5:539–551

    CAS  Google Scholar 

  80. Benowitz NL, Jacob 3rd P, Fong I, Gupta S (1994) Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine. J Pharmacol Exp Ther 268:296–303

    CAS  Google Scholar 

  81. Byrd GD, Cnang KM, Greene JM, de Bethizy JD (1992) Evidence for urinary excretion of glucuronide conjugates of nicotine, cotinine, and trans-3′-hydroxycotinine in smokers. Drug Metab Dispos 20:192–197

    CAS  Google Scholar 

  82. Schmeltz I, Hoffmann D (1977) Nitrogen containing compounds in tobacco and tobacco smoke. Chem Rev 77:295–311

    CAS  Google Scholar 

  83. Rosecrans JA, Spencer RM, Krynock GM, Chance WT (1978) Discriminative stimulus properties of nicotine and nicotine-related compounds. In: Bättig K (ed) Behavioral effects of nicotine. S. Karger, Basel, pp. 70–82

    Google Scholar 

  84. Desai RI, Barber DJ, Terry P (1999) Asymmetric generalization between the discriminative stimulus effects of nicotine and cocaine. Behav Pharmacol 10:647–656

    CAS  Google Scholar 

  85. Caine SB, Collins GT, Thomsen M, Wright C, Lanier RK, Mello NK (2014) Nicotine-like behavioral effects of the minor tobacco alkaloids nornicotine, anabasine, and anatabine in male rodents. Exp Clin Psychopharmacol 22:9–22

    CAS  Google Scholar 

  86. Dale HH (1914) The action of certain esters and ethers of choline, and their relation to muscarine. J Pharmacol Exp Ther 6:147

    CAS  Google Scholar 

  87. Langley JN (1905) On the reaction of cells and of nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curari. J Physiol 33:374–413

    Google Scholar 

  88. Langley JN (1914) The antagonism of curari and nicotine in skeletal muscle. J Physiol 48:73–108

    CAS  Google Scholar 

  89. Changeux JP (2012) The nicotinic acetylcholine receptor: the founding father of the pentameric ligand-gated ion channel superfamily. J Biol Chem 287:40207–40215

    CAS  Google Scholar 

  90. Lindstrom J, Anand R, Gerzanich V, Peng X, Wang F, Wells G (1996) Structure and function of neuronal nicotinic acetylcholine receptors. Prog Brain Res 109:125–137

    CAS  Google Scholar 

  91. Wolstenholme AJ (2012) Glutamate-gated chloride channels. J Biol Chem 287:40232–40238

    CAS  Google Scholar 

  92. Gotti C, Zoli M, Clementi F (2006) Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol Sci 27:482–491

    CAS  Google Scholar 

  93. Hurst R, Rollema H, Bertrand D (2013) Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacol Ther 137:22–54

    CAS  Google Scholar 

  94. McGehee DS, Role LW (1995) Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annu Rev Physiol 57:521–546

    CAS  Google Scholar 

  95. Corringer PJ, Le Novère N, Changeux JP (2000) Nicotinic receptors at the amino acid level. Annu Rev Pharmacol Toxicol 40:431–458

    CAS  Google Scholar 

  96. Miyazawa A, Fujiyoshi Y, Stowell M, Unwin N (1999) Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall. J Mol Biol 288:765–786

    CAS  Google Scholar 

  97. Dani JA, De Biasi M (2001) Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav 70:439–446

    CAS  Google Scholar 

  98. Kenny PJ, Markou A (2001) Neurobiology of the nicotine withdrawal syndrome. Pharmacol Biochem Behav 70:531–549

    CAS  Google Scholar 

  99. Malin DH (2001) Nicotine dependence: studies with a laboratory model. Pharmacol Biochem Behav 70:551–559

    CAS  Google Scholar 

  100. Wonnacott S (1997) Presynaptic nicotinic ACh receptors. Trends Neurosci 20:92–98

    CAS  Google Scholar 

  101. Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci 1988(85):5274–5278

    Google Scholar 

  102. Schechter MD, Meehan SM (1992) Further evidence for the mechanisms that may mediate nicotine discrimination. Pharmacol Biochem Behav 41:807–812

    CAS  Google Scholar 

  103. Corrigall WA, Coen KM (1994) Dopamine mechanisms play at best a small role in the nicotine discriminative stimulus. Pharmacol Biochem Behav 48:817–820

    CAS  Google Scholar 

  104. Rosecrans JA, Chance WT, Schechter MD (1976) The discriminative stimulus properties of nicotine, d-amphetamine and morphine in dopamine depleted rats. Psychpharmacol Commun 2:349–356

    CAS  Google Scholar 

  105. Chance WT, Kallman MD, Rosecrans JA, Spencer RM (1978) A comparison of nicotine and structurally related compounds as discriminative stimuli. Br J Pharmacol 63:609–616

    CAS  Google Scholar 

  106. Stolerman IP, Pratt JA, Garcha HS, Giardini V, Kumar R (1983) Nicotine cue in rats analysed with drugs acting on cholinergic and 5-hydroxytryptamine mechanisms. Neuropharmacology 22:1029–1037

    CAS  Google Scholar 

  107. Craft RM, Howard JL (1988) Cue properties of oral and transdermal nicotine in the rat. Psychopharmacology 96:281–284

    CAS  Google Scholar 

  108. Stolerman IP, Kumar R, Reavill C (1988) Discriminative stimulus effects of cholinergic agonists and the actions of their antagonists. Psychopharmacol Ser 1988(4):32–43

    Google Scholar 

  109. Miyata H, Ando K, Yanagita T (1991) Studies on the involvement of the nucleus accumbens in the discriminative effects of nicotine in rats. Nihon Yakurigaku Zasshi 98:389–397

    CAS  Google Scholar 

  110. Ando K, Miyata H, Hironaka N, Tsuda T, Yanagita T (1993) The discriminative effects of nicotine and their central sites in rats. Yakubutsu Seishin Kodo 13:129–136

    CAS  Google Scholar 

  111. Chandler CJ, Stolerman IP (1997) Discriminative stimulus properties of the nicotinic agonist cytisine. Psychopharmacology 129:257–264

    CAS  Google Scholar 

  112. Gasior M, Shoaib M, Yasar S, Jaszyna M, Goldberg SR (1999) Acquisition of nicotine discrimination and discriminative stimulus effects of nicotine in rats chronically exposed to caffeine. J Pharmacol Exp Ther 288:1053–1073

    CAS  Google Scholar 

  113. Mansbach RS, Chambers LK, Rovetti CC (2000) Effects of the competitive nicotinic antagonist erysodine on behavior occasioned or maintained by nicotine: comparison with mecamylamine. Psychopharmacology 148:234–242

    CAS  Google Scholar 

  114. Wiley JL, Lavecchia KL, Martin BR, Damaj MI (2002) Nicotine-like discriminative stimulus effects of bupropion in rats. Exp Clin Psychopharmacol 10:129–135

    CAS  Google Scholar 

  115. Young R, Glennon RA (2002) Nicotine and bupropion share a similar discriminative stimulus effect. Eur J Pharmacol 443:113–118

    CAS  Google Scholar 

  116. Zaniewska M, McCreary AC, Przegaliński E, Filip M (2006) Evaluation of the role of nicotinic acetylcholine receptor subtypes and cannabinoid system in the discriminative stimulus effects of nicotine in rats. Eur J Pharmacol 540:96–106

    CAS  Google Scholar 

  117. Paterson NE, Fedolak A, Oliver B, Hanania T, Ghavami A, Caldarone B (2010) Psychostimulant-like discriminative stimulus and locomotor sensitization properties of the wake-promoting agent modafinil in rodents. Pharmacol Biochem Behav 95:449–456

    CAS  Google Scholar 

  118. Paterson NE, Min W, Hackett A, Lowe D, Hanania T, Caldarone B, Ghavami A (2010) The high-affinity nAChR partial agonists varenicline and sazetidine-A exhibit reinforcing properties in rats. Prog Neuro-Psychopharmacol Biol Psychiatry 34:1455–1464

    CAS  Google Scholar 

  119. Jutkiewicz EM, Brooks EA, Kynaston AD, Rice KC, Woods JH (2011) Patterns of nicotinic receptor antagonism: nicotine discrimination studies. J Pharmacol Exp Ther 339:194–202

    CAS  Google Scholar 

  120. Cunningham CS, Javors MA, McMahon LR (2012) Pharmacologic characterization of a nicotine-discriminative stimulus in rhesus monkeys. J Pharmacol Exp Ther 341:840–849

    CAS  Google Scholar 

  121. Cunningham CS, McMahon LR (2013) Multiple nicotine training doses in mice as a basis for differentiating the effects of smoking cessation aids. Psychopharmacology 228:321–333

    CAS  Google Scholar 

  122. Stolerman IP, Chandler CJ, Garcha HS, Newton JM (1997) Selective antagonism of behavioural effects of nicotine by dihydro-beta-erythroidine in rats. Psychopharmacology 129:390–397

    CAS  Google Scholar 

  123. Gommans J, Stolerman IP, Shoaib M (2000) Antagonism of the discriminative and aversive stimulus properties of nicotine in C57BL/6J mice. Neuropharmacology 39:2840–2847

    CAS  Google Scholar 

  124. Shoaib M, Zubaran C, Stolerman IP (2000) Antagonism of stimulus properties of nicotine by dihydro-beta-erythroidine (DHβE) in rats. Psychopharmacology 149:140–146

    CAS  Google Scholar 

  125. Lee JY, Choi MJ, Choe ES, Lee YJ, Seo JW, Yoon SS (2016) Differential discriminative-stimulus effects of cigarette smoke condensate and nicotine in nicotine-discriminating rats. Behav Brain Res 306:197–201

    CAS  Google Scholar 

  126. Quarta D, Naylor CG, Barik J, Fernandes C, Wonnacott S, Stolerman IP (2009) Drug discrimination and neurochemical studies in alpha7 null mutant mice: tests for the role of nicotinic alpha7 receptors in dopamine release. Psychopharmacology 203:399–410

    CAS  Google Scholar 

  127. Ford RV, Madison JC, Moyer JH (1956) Pharmacology of mecamylamine. Am J Med Sci 232:129–143

    CAS  Google Scholar 

  128. Rose JE, Behm FM, Westman EC (1998) Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy. Exp Clin Psychopharmacol 6:331–343

    CAS  Google Scholar 

  129. Shytle RD, Penny E, Silver AA, Goldman J, Sanberg PR (2002) Mecamylamine (Inversine): an old antihypertensive with new research directions. J Hum Hypertens 16:453–457

    CAS  Google Scholar 

  130. Stolerman IP, Goldfarb T, Fink R, Jarvik ME (1973) Influencing cigarette smoking with nicotine antagonists. Psychopharmacologia 28:2472–2459

    Google Scholar 

  131. Arias HR, Targowska KM, Feuerbach D, Sullivan CJ, Maciejewski R, Jozwiak K (2010) Different interaction between tricyclic antidepressants and mecamylamine with the human alpha3beta4 nicotinic acetylcholine receptor ion channel. Neurochem Int 56:642–649

    CAS  Google Scholar 

  132. Kaiser SA, Soliakov L, Harvey SC, Luetje CW, Wonnacott S (1998) Differential inhibition by alpha-conotoxin-MII of the nicotinic stimulation of [3H]dopamine release from rat striatal synaptosomes and slices. J Neurochem 70:1069–1076

    CAS  Google Scholar 

  133. Papke RL, Wecker L, Stitzel JA (2010) Activation and inhibition of mouse muscle and neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. J Pharmacol Exp Ther 333:501–518

    CAS  Google Scholar 

  134. Chavez-Noriega LE, Crona JH, Washburn MS, Urrutia A, Elliott KJ, Johnson EC (1997) Pharmacological characterization of recombinant human neuronal nicotinic acetylcholine receptors h alpha 2 beta 2, h alpha 2 beta 4, h alpha 3 beta 2, h alpha 3 beta 4, h alpha 4 beta 2, h alpha 4 beta 4 and h alpha 7 expressed in Xenopus oocytes. J Pharmacol Exp Ther 280:346–356

    CAS  Google Scholar 

  135. Harvey SC, Maddox FN, Luetje CW (1996) Multiple determinants of dihydro-beta-erythroidine sensitivity on rat neuronal nicotinic receptor alpha subunits. J Neurochem 67:1953–1959

    CAS  Google Scholar 

  136. Papke RL, Dwoskin LP, Crooks PA, Zheng G, Zhang Z, McIntosh JM, Stokes C (2008) Extending the analysis of nicotinic receptor antagonists with the study of alpha6 nicotinic receptor subunit chimeras. Neuropharmacology 54:1189–1200

    CAS  Google Scholar 

  137. Verbitsky M, Rothlin CV, Katz E, Elgoyhen AB (2000) Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor. Neuropharmacology 39:2515–2524

    CAS  Google Scholar 

  138. Harbourne JB, Baxter H (1993) Phytochemical dictionary. Taylor & Francis, London, p. 153

    Google Scholar 

  139. Absalom NL, Quek G, Lewis TM, Qudah T, von Arenstorff I, Ambrus JI, Harpsøe K, Karim N, Balle T, McLeod MD, Chebib M (2013) Covalent trapping of methyllycaconitine at the α4-α4 interface of the α4β2 nicotinic acetylcholine receptor: antagonist binding site and mode of receptor inhibition revealed. J Biol Chem 288:26521–26532

    CAS  Google Scholar 

  140. Capelli AM, Castelletti L, Chen YH, Van der Keyl H, Pucci L, Oliosi B, Salvagno C, Bertani B, Gotti C, Powell A, Mugnaini M (2011) Stable expression and functional characterization of a human nicotinic acetylcholine receptor with α6β2 properties: discovery of selective antagonists. Br J Pharmacol 163:313–329

    CAS  Google Scholar 

  141. Mogg AJ, Whiteaker P, McIntosh JM, Marks M, Collins AC, Wonnacott S (2002) Methyllycaconitine is a potent antagonist of alpha-conotoxin-MII-sensitive presynaptic nicotinic acetylcholine receptors in rat striatum. J Pharmacol Exp Ther 302:197–204

    CAS  Google Scholar 

  142. Overton DA (1974) Experimental methods for the study of state-dependent learning. Fed Proc 33:1800–1813

    CAS  Google Scholar 

  143. Frey LG, Winter JC (1978) Current trends in the study of drugs as discriminative stimuli. In: Ho BT, Richards III DW, Chute DL (eds) Drug discrimination and state dependent learning. Academic Press, New York, pp. 35–45

    Google Scholar 

  144. Garcha HS, Stolerman IP (1993) Discriminative stimulus effects of the nicotine antagonist mecamylamine in rats. J Psychopharmacol 7:43–51

    CAS  Google Scholar 

  145. Cunningham CS, Moerke MJ, McMahon LR (2014) The discriminative stimulus effects of mecamylamine in nicotine-treated and untreated rhesus monkeys. Behav Pharmacol 25:296–305

    CAS  Google Scholar 

  146. Kumar R, Reavill C, Stolerman IP (1987) Nicotine cue in rats: effects of central administration of ganglion-blocking drugs. Br J Pharmacol 90:239–246

    CAS  Google Scholar 

  147. Hughes JR, Gulliver SB, Fenwick JW, Valliere WA, Cruser K, Pepper S, Shea P, Solomon LJ, Flynn BS (1992) Smoking cessation among self-quitters. Health Psychol 11:331–334

    CAS  Google Scholar 

  148. Raw M, McNeill A, West R (1998) Smoking cessation guidelines for health professionals. A guide to effective smoking cessation interventions for the health care system. Health education authority. Thorax 53(Suppl 5 Pt 1):S1–19

    Google Scholar 

  149. Britton J, Jarvis MJ (2000) Bupropion: a new treatment for smokers. Nicotine replacement treatment should also be available on the NHS. BMJ 321:65–66

    CAS  Google Scholar 

  150. Damaj MI, Patrick GS, Creasy KR, Martin BR (1997) Pharmacology of lobeline, a nicotinic receptor ligand. J Pharmacol Exp Ther 282:410–419

    CAS  Google Scholar 

  151. Dwoskin LP, Crooks PA (2001) Competitive neuronal nicotinic receptor antagonists: a new direction for drug discovery. J Pharmacol Exp Ther 298:395–402

    CAS  Google Scholar 

  152. Kaniaková M, Lindovský J, Krůšek J, Adámek S, Vyskočil F (2011) Dual effect of lobeline on α4β2 rat neuronal nicotinic receptors. Eur J Pharmacol 658:108–113

    Google Scholar 

  153. Miller DK, Crooks PA, Dwoskin LP (2000) Lobeline inhibits nicotine-evoked [(3)H]dopamine overflow from rat striatal slices and nicotine-evoked (86)Rb(+) efflux from thalamic synaptosomes. Neuropharmacology 39:2654–2662

    CAS  Google Scholar 

  154. Miller DK, Harrod SB, Green TA, Wong MY, Bardo MT, Dwoskin LP (2003) Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats. Pharmacol Biochem Behav 74:279–286

    CAS  Google Scholar 

  155. Department of Health and Human Services, Food and drug Administration (1993) Smoking deterrent drug products for over-the-counter human use. Federal Register 58(103):31236–31241

    Google Scholar 

  156. Sachs DP (1986) Cigarette smoking. Health effects and cessation strategies. Clin Geriatr Med 2:337–362

    CAS  Google Scholar 

  157. U.S Department of Health and Human Services (1988) The health consequences of smoking: nicotine addiction. A report of the Surgeon General. Office on Smoking and Health, Maryland

    Google Scholar 

  158. Cunningham CS, Polston JE, Jany JR, Segert IL, Miller DK (2006) Interaction of lobeline and nicotinic receptor ligands with the discriminative stimulus properties of cocaine and amphetamine. Drug Alcohol Depend 84:211–222

    CAS  Google Scholar 

  159. Desai RI, Barber DJ, Terry P (2003) Dopaminergic and cholinergic involvement in the discriminative stimulus effects of nicotine and cocaine in rats. Psychopharmacology 167:335–343

    CAS  Google Scholar 

  160. Miller DK, Crooks PA, Teng L, Witkin JM, Munzar P, Goldberg SR, Acri JB, Dwoskin LP (2001) Lobeline inhibits the neurochemical and behavioral effects of amphetamine. J Pharmacol Exp Ther 296:1023–1034

    CAS  Google Scholar 

  161. Desai RI, Bergman J (2014) Drug discrimination in methamphetamine-trained rats: effects of cholinergic nicotinic compounds. J Pharmacol Exp Ther 335:807–816

    Google Scholar 

  162. Reavill C, Walther B, Stolerman IP, Testa B (1990) Behavioural and pharmacokinetic studies on nicotine, cytosine and lobeline. Neuropharmacology 29:619–624

    CAS  Google Scholar 

  163. Balfour DJ (2001) The pharmacology underlying pharmacotherapy for tobacco dependence: a focus on bupropion. Int J Clin Pract 55:53–57

    CAS  Google Scholar 

  164. Harrison C (2001) Bupropion may not be as good as editorial implies. Br Med J 322:431

    CAS  Google Scholar 

  165. Hurt RD, Sachs DPL, Glover ED, Offord KP, Johnston JA, Dale LC, Khayrallah MA, Schroeder DR, Glover PN, Sullivan CR, Croghan IT, Sullivan PM (1997) A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 337:1195–1202

    CAS  Google Scholar 

  166. Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA (1999) A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 340:685–691

    CAS  Google Scholar 

  167. Butz RF, Welch RM, Findlay JWA (1982) Relationship between bupropion disposition and dopamine uptake inhibition in rats and mice. J Pharmacol Exp Ther 221:676–685

    CAS  Google Scholar 

  168. Dufrensne RL, Weber SS, Becker RE (1984) Bupropion hydrochloride. Drug Intell Clin Pharm 18:957–964

    Google Scholar 

  169. Dufrensne RL, Becker RE, Blitzer R, Wagner RL, Lal H (1985) Safety and efficacy of bupropion, a novel antidepressant. Drug Dev Res 6:39–45

    Google Scholar 

  170. Ferris RM, Maxwell RA, Cooper BR, Soroko FE (1982) Neurochemical and neuropharmacological investigations into the mechanisms of action of bupropion. HCI—a new atypical antidepressant agent. Adv Biochem Psycholpharmacol 31:277–286

    CAS  Google Scholar 

  171. Fryer JD, Lukas RJ (1999) Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencylidine and ibogaine. J Pharmacol Exp Ther 288:88–92

    CAS  Google Scholar 

  172. Slemmer JE, Martin BR, Damaj MI (2000) Bupropion is a nicotinic antagonist. J Pharmacol Exp Ther 295:321–327

    CAS  Google Scholar 

  173. Jones CN, Howard JL, McBennett ST (1980) Stimulus properties of antidepressants in the rat. Psychopharmacology 67:111–118

    CAS  Google Scholar 

  174. Blitzer RD, Becker RE (1985) Characterization of the bupropion cue in the rat: lack of evidence for a dopaminergic mechanism. Psychopharmacology 85:173–177

    CAS  Google Scholar 

  175. Terry P, Katz JL (1997) Dopaminergic mediation of the discriminative stimulus effects of bupropion in rats. Psychopharmacology 134:201–212

    CAS  Google Scholar 

  176. Evans SM, Johanson CE (1987) Amphetamine-like effects of anorectics and related compounds in pigeons. J Pharmacol Exp Ther 241:817–825

    CAS  Google Scholar 

  177. de la Garza R, Johanson CE (1987) Discriminative stimulus properties of intragastrically administered d-amphetamine and pentobarbital in rhesus monkeys. J Pharmacol Exp Ther 243:955–962

    Google Scholar 

  178. Kamien JB, Woolverton WL (1989) A pharmacological analysis of the discriminative stimulus properties of d-amphetamine in rhesus monkeys. J Pharmacol Exp Ther 248:938–946

    CAS  Google Scholar 

  179. Rush CR, Kollins SH, Pazzaglia PJ (1998) Discriminative-stimulus and participant-rated effects of methylphenidate, bupropion, and triazolam in d-amphetamine-trained humans. Exp Clin Psychopharmacol 6:32–44

    CAS  Google Scholar 

  180. Bondarev ML, Bondareva TS, Young R, Glennon RA (2003) Behavioral and biochemical investigations of bupropion metabolites. Eur J Pharmacol 474:85–93

    CAS  Google Scholar 

  181. Heal DJ, Frankland AT, Gosden J, Hutchins LJ, Prow MR, Luscombe GP, Buckett WR (1992) A comparison of the effects of sibutramine hydrochloride, bupropion and methamphetamine on dopaminergic function: evidence that dopamine is not a pharmacological target for sibutramine. Psychopharmacology 107:303–309

    CAS  Google Scholar 

  182. Banks ML, Smith DA, Blough BE (2016) Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxyl metabolites in male rhesus monkeys. Behav Pharmacol 27:196–203

    CAS  Google Scholar 

  183. Makhay MM, O’Donnell JM (1999) Effects of antidepressants in rats trained to discriminate the beta-2 adrenergic agonist clenbuterol. Pharmacol Biochem Behav 63:319–324

    CAS  Google Scholar 

  184. Lamb RJ, Griffiths RR (1990) Self-administration in baboons and the discriminative stimulus effects in rats of bupropion, nomifensine, diclofensine and imipramine. Psychopharmacology 102:183–190

    CAS  Google Scholar 

  185. Kleven MS, Anthony EW, Woolverton WL (1990) Pharmacological characterization of the discriminative stimulus effects of cocaine in rhesus monkeys. J Pharmacol Exp Ther 254:312–317

    CAS  Google Scholar 

  186. Johanson CE, Barrett JE (1993) The discriminative stimulus effects of cocaine in pigeons. J Pharmacol Exp Ther 267:1–8

    CAS  Google Scholar 

  187. Broadbent J, Gaspard TM, Dworkin SI (1995) Assessment of the discriminative stimulus effects of cocaine in the rat: lack of interaction with opioids. Pharmacol Biochem Behav 51:379–385

    CAS  Google Scholar 

  188. Baker LE, Riddle EE, Saunders RB, Appel JB (1993) The role of monoamine uptake in the discriminative stimulus effects of cocaine and related compounds. Behav Pharmacol 4:69–79

    CAS  Google Scholar 

  189. Quinton MS, Gerak LR, Moerschbaecher JM, Winsauer PJ (2006) Effects of pregnanolone in rats discriminating cocaine. Pharmacol Biochem Behav 85:385–392

    CAS  Google Scholar 

  190. Awasaki Y, Nojima H, Nishida N (2011) Application of the conditioned taste aversion paradigm to assess discriminative stimulus properties of psychostimulants in rats. Drug Alcohol Depend 118:288–294

    CAS  Google Scholar 

  191. McMillan DE, Li M, Shide DJ (1999) Differences between alcohol-preferring and alcohol-nonpreferring rats in ethanol generalization. Pharmacol Biochem Behav 64:415–419

    CAS  Google Scholar 

  192. Melia KF, Spealman RD (1991) Pharmacological characterization of the discriminative-stimulus effects of GBR 12909. J Pharmacol Exp Ther 258:626–632

    CAS  Google Scholar 

  193. Zhang L, Barrett JE (1991) Imipramine as a discriminative stimulus. J Pharmacol Exp Ther 259:1088–1093

    CAS  Google Scholar 

  194. Crissman AM, O’Donnell JM (2002) Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol. J Pharmacol Exp Ther 302:606–611

    CAS  Google Scholar 

  195. Mori T, Uzawa N, Kazawa H, Watanabe H, Mochizuki A, Shibasaki M, Yoshizawa K, Higashiyama K, Suzuki T (2014) Differential substitution for the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats. J Pharmacol Exp Ther 350:403–411

    Google Scholar 

  196. Sasaki JE, Tatham TA, Barrett JE (1995) The discriminative stimulus effects of methamphetamine in pigeons. Psychopharmacology 120:303–310

    CAS  Google Scholar 

  197. Munzar P, Goldberg SR (2000) Dopaminergic involvement in the discriminative-stimulus effects of methamphetamine in rats. Psychopharmacology 148:209–216

    CAS  Google Scholar 

  198. Dekeyne A, Millan MJ (2009) Discriminative stimulus properties of the atypical antidepressant, mirtazapine, in rats: a pharmacological characterization. Psychopharmacology 203:329–341

    CAS  Google Scholar 

  199. Shoaib M, Sidhpura N, Shafait S (2003) Investigating the actions of bupropion on dependence-related effects of nicotine in rats. Psychopharmacology 165:405–412

    CAS  Google Scholar 

  200. Damaj MI, Grabus SD, Navarro HA, Vann RE, Warner JA, King LS, Wiley JL, Blough BE, Lukas RJ, Carroll FI (2010) Effects of hydroxymetabolites of bupropion on nicotine dependence behavior in mice. J Pharmacol Exp Ther 334:1087–1095

    CAS  Google Scholar 

  201. de la Garza R, Evans S, Johanson CE (1987) Discriminative stimulus properties of oxazepam in the pigeon. Life Sci 40:71–79

    Google Scholar 

  202. Schulze DR, Carroll FI, McMahon LR (2012) Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys. Psychopharmacology 222:425–438

    CAS  Google Scholar 

  203. Golden RN, James SP, Sherer MA, Rudorfer MV, Sack DA, Potter WZ (1985) Psychoses associated with bupropion treatment. Am J Psychiatry 142:1459–1462

    CAS  Google Scholar 

  204. Glaxo Wellcome (2001) Zyban® (bupropion hydrochloride) sustained-release tablets. Product information

    Google Scholar 

  205. Miller L, Griffith J (1983) A comparison of bupropion, dextramphetamine, and placebo in mixed-substance abusers. Psychopharmacology 80:199–205

    CAS  Google Scholar 

  206. Schroeder DH (1983) Metabolism and kinetics of bupropion. J Clin Psychiatry 44:79–81

    CAS  Google Scholar 

  207. Horst WD, Preskorn SH (1998) Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion. J Affect Disord 51:237–254

    CAS  Google Scholar 

  208. Rotzinger S, Bourin M, Akimoto Y, Coutts RT, Baker GB (1999) Metabolism of some “second”- and “fourth”-generation antidepressants: iprindole, viloxazine, bupropion, mianserin, maprotiline, trazodone, nefazodone, and venlafaxine. Cell Mol Neurobiol 19:427–442

    CAS  Google Scholar 

  209. Suckow RF, Smith TM, Perumal AS, Cooper TB (1986) Pharmacokinetics of bupropion and metabolites in plasma and brain of rats, mice, and guinea pigs. Drug Metab Dispos 14:692–697

    CAS  Google Scholar 

  210. Welch RM, Lai AA, Schroeder DH (1987) Pharmacological significance of the species differences in bupropion metabolism. Xenobiotica 17:287–298

    CAS  Google Scholar 

  211. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley 3rd FD, O’Neill BT (2005) Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 48:3474–3477

    CAS  Google Scholar 

  212. Mihalak KB, Carroll FI, Lueje CW (2006) Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol 70:801–805

    CAS  Google Scholar 

  213. Gould RW, Czoty PW, Nader SH, Nader MA (2011) Effects of varenicline on the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys. J Pharmacol Exp Ther 339:678–686

    CAS  Google Scholar 

  214. Smith JW, Mogg A, Tafi E, Peacey E, Pullar IA, Szekeres P, Tricklebank M (2007) Ligands selective for α4β2 but not α3β4 or α7 nicotinic receptors generalise to the nicotine discriminative stimulus in the rat. Psychopharmacology 190:157–170

    CAS  Google Scholar 

  215. Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA, Lu Y, Mansbach RS, Mather RJ, Rovetti CC, Sands SB, Schaeffer E, Schulz DW, Tingley 3rd FD, Williams KE (2007) Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology 52:985–994

    CAS  Google Scholar 

  216. LeSage MG, Shelley D, Ross JT, Carroll FI, Corrigall WA (2009) Effects of the nicotinic receptor partial agonists varenicline and cytisine on the discriminative stimulus effects of nicotine in rats. Pharmacol Biochem Behav 91:461–467

    CAS  Google Scholar 

  217. Le Foll B, Chakraborty-Chtterjee M, Lev-Ran S, Barnes C, Pushparaj A, Gamaleddin I, Yan Y, Khaled M, Goldberg SR (2012) Varenicline decreases nicotine self-administration and cue-induced reinstatement of nicotine-seeking behaviour in rats when a long pretreatment time is used. Int J Neuropsychopharmacol 15:1265–1274

    Google Scholar 

  218. Rodriguez JS, Cunningham CS, Moura FB, Ondachi P, Carroll FI, McMahon LR (2014) Discriminative stimulus and hypothermic effects of some derivatives of the nAChR agonist epibatidine in mice. Psychopharmacology 231:4455–4466

    CAS  Google Scholar 

  219. Harris CM, Emmett-Oglesby MW, Robinson NG, Lal H (1986) Withdrawal from chronic nicotine substitutes partially for the interoceptive stimulus produced by pentylenetetrazol (PTZ). Psychopharmacology 90:85–89

    CAS  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the helpful comments and suggestions provided by Dr. John R. James.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980613, Richmond, VA, 23298-0613, USA

    John A. Rosecrans

  2. Department of Medicinal Chemistry, Virginia Commonwealth University, 800 East Leigh Street, P.O. Box 980540, Richmond, VA, 23219-0540, USA

    Richard Young

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  1. Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA

    Joseph H. Porter

  2. Department of Psychological Science, Northern Michigan University, Marquette, MI, USA

    Adam J. Prus

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Rosecrans, J.A., Young, R. (2017). Discriminative Stimulus Properties of S(−)-Nicotine: “A Drug for All Seasons”. In: Porter, J.H., Prus, A.J. (eds) The Behavioral Neuroscience of Drug Discrimination. Current Topics in Behavioral Neurosciences, vol 39. Springer, Cham. https://doi.org/10.1007/7854_2017_3

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