Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent Nicotine+Cocaine self-administration

Neuropsychopharmacology

Volumn 39, Issue 5, 2014, Pages 1222-1231

  Mello, Nancy K ^a   Fivel, Peter A ^a   Kohut, Stephen J ^a   Carroll, F Ivy ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b RTI INTERNATIONAL   (United States)

Author keywords

cocaine; nicotine; nicotine addiction; polydrug abuse model; varenicline

Indexed keywords

COCAINE; NICOTINE; SODIUM CHLORIDE; VARENICLINE; BENZAZEPINE DERIVATIVE; DOPAMINE UPTAKE INHIBITOR; NICOTINIC AGENT; QUINOXALINE DERIVATIVE;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG DOSE REDUCTION; DRUG SELF ADMINISTRATION; FEMALE; LONG TERM CARE; MALE; NONHUMAN; PRIORITY JOURNAL; RHESUS MONKEY; TOBACCO DEPENDENCE; TREATMENT DURATION; ANIMAL; COCAINE-RELATED DISORDERS; DRUG EFFECTS; DRUG SEEKING BEHAVIOR; FEEDING BEHAVIOR; INSTRUMENTAL CONDITIONING; MOTIVATION; REINFORCEMENT; TOBACCO USE DISORDER;

ANIMALS; BENZAZEPINES; COCAINE; COCAINE-RELATED DISORDERS; CONDITIONING, OPERANT; DOPAMINE UPTAKE INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG-SEEKING BEHAVIOR; FEEDING BEHAVIOR; FEMALE; MACACA MULATTA; MALE; MOTIVATION; NICOTINE; NICOTINIC AGONISTS; QUINOXALINES; REINFORCEMENT (PSYCHOLOGY); SELF ADMINISTRATION; TOBACCO USE DISORDER;

EID: 84896392278     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2013.325     Document Type: Article

References (97)

1. Andreoli M, Tessari M, Pilla M, Valerio E, Hagan JJ, Heidbreder CA (2003). Selective antagonism at dopamine D3 receptors prevents nicotine-triggered relapse to nicotine-seeking behavior. Neuropsychopharmacology 28: 1272-1280. (Pubitemid 41070897)
2. Bechtholt AJ, Mark GP (2002). Enhancement of cocaine-seeking behavior by repeated nicotine exposure in rats. Psychopharmacology (Berl) 162: 178-185. (Pubitemid 34743957)
3. Benowitz NL (2009). Pharmacology of nicotine: addiction, smokinginduced disease, and therapeutics. Annu Rev Phys Chem 49: 57-71.
4. Bordia T, Hrachova M, Chin M, McIntoch JM, Quik M (2012). Varenicline is a potent partial agonist at a6b2* nicotinic acetylcholine receptors in rat and monkey striatum. J Pharmacol Exp Ther 342: 327-334.
5. Budney AJ, Higgins ST, Hughes JR, Bickel WK (1993). Nicotine and caffeine use in cocaine-dependent individuals. J Subst Abuse 5: 117-130.
6. CDC(2002). Cigarette smoking among adults-United States.2000.
7. MMWR Morb Mortal Weekly Report 51: 642-645.
8. CDC (2004). Adult cigarette smoking in the United States: current estimates. National Center for Chronic Disease Prevention and Health Promotion Tobacco Information and Prevention Source (TIPS) 15: 20-58.
9. CDC (2005). Annual smoking-attributable mortality, years of potential life ost and productivity losses-United States, 1997-2001. MMWR Morb Mortal Weekly Report 54: 625-628.
10. Cinciripini PM, Robinson JD, Karam-Hage M, Minnix JA, Lam C, Versace F et al (2013). Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on proloonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. JAMA Psychiatry 70: 522-533.
11. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J et al (2005). Varenicline: an a4b2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 48: 3474-3477. (Pubitemid 40664098)
12. 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. (Pubitemid 24252850)
13. DAWN (2010). Drug Abuse Warning Network, 2010: Area Profiles of Drug-Related Mortality. Substance Abuse and Mental Health Services Administration: Rockville, MDVol Series D-36. HHS Publication No. (SMA) 12-4699, 294 pp.
14. DiChiara G (2000). Role of dopamine in the behavioural actions of nicotine related to addiction (In Process Citation). Eur J Pharmacol 393: 295-314.
15. DiChiara G, Imperato A (1988). Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumens and in the dorsal caudate of freely moving rats. J Pharmacol Exp Ther 244: 1067-1080. (Pubitemid 18090131)
16. DiChiara G, Imperato A (1988a). Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85: 5274-5278.
17. Exley R, Clements MA, Hartung H, McIntosh JM, Franklin M, Bermudez I et al (2013). Striatal dopamine transmission is reduced after chronic nicotine with a decrease in a6-nicotinic receptor control in nucleus accumbens. Eur J Neurosc 10 July 2013. doi:10.1111/ejn.12298 (e-pub ahead of print).
18. Faessel HM, Obach RS, Rollema H, Ravva P, Williams KE, Burstein AH (2010). A review of the clinical pharmacokinetics and pharmacodynamics of varenicline for smoking cessation. Clin Pharmacokinet 49: 799-816.
19. Fivel PA (2011). Computer-controlled drug doses for IV drug selfadministration. Exp Clin Psychopharmacol 19: 131-133.
20. Freeman KB, Woolverton WL (2009). Self-administration of cocaine and nicotine mixtures by rhesus monkeys. Psychopharmacology 207: 99-106. (Pubitemid 43668315)
21. George O, Lloyd A, Carroll FI, Damaj MI, Koob GF (2011). Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration. Psychopharmacology 213: 715-722.
22. Gerasimov MR, Franceschi M, Volkow ND, Rice O, Schiffer WK, Dewey SL (2000). Synergistic interactions between nicotine and cocaine or methylphenidate depend on the dose of dopamine transporter inhibitor. Synapse 38: 432-437.
23. Gotti C, Clementi F (2004). Neuronal nicotinic receptors: from structure to pathology. Prog Neurobiol 74: 363-396. (Pubitemid 40092737)
24. Gotti C, Moretti M, Gaimarri A, Zanardi A, Clementi F, Zoli M (2007). Heterogeneity and complexity of native brain nicotinic receptors. Biochem Pharm 74: 1102-1111. (Pubitemid 47432651)
25. 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.
26. Grady SR, Drenan RM, Breining SR, Yohannes D, Wageman CR, Federov NB et al (2010). Structural differences determine the relative selectivity of nicotinic compounds for native alpha 4 beta 2*-, alpha 6 beta 2*-, alpha 3 beta 4*-and alpha 7-nicotine acetylcholine receptors. Neuropharmacology 58: 1054-1066.
27. Guillem K, Peoples LL (2010). Varenicline effects on cocaine self administration and reinstatement behavior. Biochem Pharm 21: 96-103.
28. Han ZY, Le Novere N, Zoli M, Hill JAJ, Champtiaux N, Changeux JP (2000). Localization of nAChR subunit mRNAs in the brain of macaca mulatta. Eur J Neurosc 12: 3664-3674.
29. Han ZY, Zoli M, Cardona A, Bourgeois JP, Changeux JP, Le Novere N (2003). Localization of [3H]Nicotine, [3H]Cytisine, [3H]Epibatidine, and [125I]a-Bungarotoxin Binding Sites in the Brain of Macaca mulatta. J Comp Neurol 461: 49-60. (Pubitemid 36578596)
30. Hawk LWJ, Ashare RL, Lohnes SF, Schlienz nJ, Rhodes JD, Tiffany ST et al (2012). The effects of extended pre-quit varenicline treatment on smoking behavior and short-term abstinence: a randomized clinical trial. Clin Pharmacol Ther 91: 172-180.
31. Hays JT, Ebbert JO, Sood A (2008). Efficacy and safety of varenicline for smoking cessation. Am J Med 121: S32-S42. (Pubitemid 351380541)
32. Heidbreder CA, Gardner EL, Xi Z-X, Thanos PK, Mugnaini M, Hagan JJ et al (2005). The role of central dopamine D3 receptors in drug addiciton: a review of pharmacological evidence. Brain Res Rev 49: 77-105. (Pubitemid 40800164)
33. Heidbreder CA, Newman AH (2010). Current perspectives on selective dopamine D3 receptor antagonists as pharmacotherapeutics for addictions and related disorders. Ann NY Acad Sci 1187: 4-34.
34. Henningfield JE, Shiffman S, Ferguson SG, Gritz ER (2009). Tobacco dependence and withdrawal: science base, challenges and opportunities for pharmacotherapy. Pharmacol Ther 123: 1-16.
35. Horger BA, Giles MK, Schenk S (1992). Preexposure to amphetamine and nicotine predisposes rats to self-administer a low dose of cocaine. Psychopharmacology (Berl) 107: 271-276.
36. Jorenby DE, Hays LT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE et al (2006). Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustainedrelease bupropion for smoking cessation: a randomized controlled trial. J Am Med Assoc 296: 56-63.
37. Jutkiewicz EM, Brooks EA, Kynaston AD, Rice KC, Woods JH (2011). Patterns of nicotinic receptor antagonism: Nicotine discriminative studies. J Pharmacol Exp Ther 380: 194-203.
38. Khaled MATM, Araki KF, Li B, Coen KM, Marinelli PW, Varga J et al (2010). The selective dopamine D3 receptor antagonist SB-277011A, but not the partial agonist BP 897, blocks cue-induced reinstatement of nicotine-seeking. Int J Neuropsychopharmacol 13: 181-190.
39. Koob GFLeMoal M (eds) (2006). Neurobiology of Addiction. Academic Press: London, pp 490.
40. Kuhar MJ, Ritz MC, Boja JW (1991). The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci 14: 299-302.
41. Le Foll B, Chakraborty-Chatterjee M, Lev-Ran S, Barnes C, Pushparaj A, Gamaleddin I et al (2011). Varenicline decreases nicotine self-administration and cue-induced reinstatement of nicotine-seeking behaviour in rats when a long pretreatment time is used. Int J Neuropsychopharmacology 15: 1265-1274.
42. Le Foll B, Goldberg SR, Sokoloff P (2005). D3 receptor and drug dependence: effects on reward or beyond? Neuropharmacology 49: 525-541. (Pubitemid 41169976)
43. Le Foll B, Goldberg SR, Sokoloff P (2007). Dopamine D3 receptor ligands for the treatment of tobacco dependence. Expert Opin Investig 16: 45-57. (Pubitemid 44964166)
44. 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.
45. Levin ED, Petro A, Rezvani AH, Pollard N, Christopher NC, Strauss M et al (2009). Nicotinic a7 or b2-containing receptor knockout: Effects on radial-arm maze learning and long-term nicotine consumption in mice. Behav Brain Res 196: 207-213.
46. Levine A, Huang Y, Drisaldi B, Griffin EA, Pollack DD, Xu S et al (2011). Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine. Sci Transl Med 3: 107-109.
47. Line SW (1987). Environmental enrichment for laboratory primates. J Am Vet Med Assoc 190: 854-859.
48. Mello NK, Marian W. (2005).Fischman Memorial Lecture (2004). Evaluation of drug abuse treatment medications: Concordance between clinical and preclinical studies. In: Dewey WL (ed) Problems of Drug Dependence 2004: Proceedings of the 66th Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc. U.S. Department of Health and Human Services, National Institutes of Health: Bethesda, MD, pp 82-104.
49. Mello NK, Fivel PA, Kohut SJ (2013a). Effects of chronic buspirone treatment on nicotine and concurrent nicotine\+cocaine selfadministration. Neuropsychopharmacology 38: 1264-1275.
50. Mello NK, Fivel PA, Kohut SJ, Bergman J (2013b). Effects of chronic buspirone treatment on cocaine self-administration. Neuropsychopharmacology 38: 455-467.
51. Mello NK, Mendelson JH (2013). Cocaine and other commonly abused drugs. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J (eds) Harrison's Principles of Internal Medicine. 19th Edition McGraw-Hill Co.: New York, (in press).
52. Mello NK, Mendelson JH, Kelly M, Diaz-Migoyo N, Sholar JW (1997). The effects of chronic cocaine self-administration on the menstrual cycle in rhesus monkeys. J Pharmacol Exp Ther 281: 70-83. (Pubitemid 27203053)
53. Mello NK, Negus SS (1996). Preclinical evaluation of pharmacotherapies for treatment of cocaine and opiate abuse using drug self-administration procedures. Neuropsychopharmacology 14: 375-424. (Pubitemid 26271172)
54. Mello NK, Negus SS, Lukas SE, Mendelson JH, Sholar JW, Drieze JM (1995). A primate model of polydrug abuse: cocaine and heroin combinations. J Pharmacol Exp Ther 274: 1325-1337.
55. Mello NK, Newman JL (2011). Discriminative and reinforcing stimulus effects of nicotine, cocaine, and cocaine\+nicotine combinations in rhesus monkeys. Exp Clin Psychopharmacol 19: 203-214.
56. Mihalak KB, Carroll FI, Luetje CW (2006). Varenicline is a partial agonist at a4b2 and a full agonist at a7 neuronal nicotinic receptors. Mol Pharmacol 70: 801-805. (Pubitemid 44268437)
57. Negus SS, Mello NK (2003). Effects of chronic d-amphetamine treatment on cocaine-and food-maintained responding under a second-order schedule in rhesus monkeys. Drug Alc Depend 70: 39-52. (Pubitemid 36385152)
58. Newman AH, Blaylock BL, Nader MA, Bergman J, Sibley DR, Skolnick P (2012). Medication discovery for addiction: Translating the dopamine D3 receptor hypothesis. Biochem Pharm 84: 992-890.
59. Newman AH, Grundt P, Cyriac G, Deschamps JR, Taylor M, Kumar R et al (2009). N-(4-(4-(2,3-Dichloro-or 2-methoxyphenyl)piperazin-1-yl)butyl) heterobiarylcarboxamides with functionalized linking chains as high affinity and enantioselective D3 receptor antagonists. J Med Chem 52: 2559-2570.
60. Newman AH, Grundt P, Nader MA (2005). Dopamine D3 receptor partial agonists and antagonists as potential drug abuse therapeutic agents. J Med Chem 48: 3663-3679. (Pubitemid 40776839)
61. Newman JL, Negus SS, Lozama A, Prisinzano TE, Mello NK (2010). Behavioral evaluation of modafinil and the abuse-related effects of cocaine in rhesus monkeys. Exp Clin Psychopharmacol 18: 395-408.
62. Niaura R, Jones C, Kirkpatrick P (2006). Varenicline. Nature Rev 5: 537-538.
63. Nisell M, Nomikos GG, Svensson TH (1994). Systemic nicotineinduced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental area. Synapse 16: 36-44. (Pubitemid 24013237)
64. O'Connor EC, Parker D, Rollema H, Mead AN (2010). The alpha4beta2 nicotinic acetylcholine-receptor partial agonist varenicline inhibits both nicotine self-administration following repeated dosing and reinstatement of nicotine seeking in rats. Psychopharmacology 208: 365-376.
65. Pak AC, Ashby CR, Heidbreder CA, Pilla M, Gilbert JG, Xi X-Z et al (2006). The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotinepaired environmental cue functions. Int J Neuropsychopharmacol 9: 1-18.
66. Paterson NE, Min W, Hackett A, Lowe D, Hanania T, Caldarone BJ et al (2010). The high-affinity nAChR agonists varenicline and sazetidine-A exhibit reinforcing properties in rats. Prog Neuropsychopharmacol & Biol Psych 34: 1455-1464.
67. Pettit HO, Justice JB (1991). Effect of dose on cocaine selfadministration behavior and dopamine levels in the nucleus accumbens. Brain Res 539: 94-102.
68. Picciotto MR, Zoli M, Rimondini R, Lena C, Marubio LM, Pich EM et al (1998). Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 391: 173-177. (Pubitemid 28092475)
69. Pich EM, Pagliusi SR, Tessari M, Talabot-Ayer D, Hooft van Huijsduijnen R, Chiamulera C (1997). Common neural substrates for the addictive properties of nicotine and cocaine. Science 275: 83-86. (Pubitemid 27020313)
70. Pierce RC, Kumaresan V (2006). The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 30: 215-238. (Pubitemid 41821810)
71. Plebani JG, Lynch KG, Yu Q, Pettinati HM, O'Brien CP, Kampman KM (2012). Results of an initial clinical trial of varenicline for the treatment of cocaine dependence. Drug Alc Depend 121: 163-166.
72. Poling J, Rounsaville B, Gonsai K, Severino K, Sofuoglu M (2010). The safety and efficacy of varenicline in cocaine using smokers maintained on methadone: a pilot study. Am J Addict 19: 401-408.
73. Pollock JD, Koustova E, Hoffman A, Shurtleff D, Volkow ND (2009). Treatments for nicotine addiction should be a top priority. Lancet 374: 513-514.
74. Quik M, Wonnacott S (2011). a6b2* and a4b2* nicotinic acetylcholine receptors as drug targets for Parkinson's Disease. Pharmacol Rev 63: 938-966.
75. Reichel CM, Murray JE, Barr JD, Bevins RA (2010). Extinction with varenicline and nornicotine, but not ABT-418, weakens conditioned responding evoked by the interoceptive stimulus effects of nicotine. Neuropharmacology 58: 1237-1245.
76. Reid MS, Mickalian JD, Delucchi KL, Berger SP (1999). A nicotine antagonist, mecamylamine, reduces cue-induced cocaine craving in cocaine-dependent subjects. Neuropsychopharmacology 20: 297-307. (Pubitemid 29067409)
77. Reid MS, Mickalian JD, Delucchi KL, Hall SM, Berger SP (1998). An acute dose of nicotine enhances cue-induced cocaine craving. Drug Alc Depend 49: 95-104. (Pubitemid 28111896)
78. Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987). Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237: 1219-1223. (Pubitemid 17131228)
79. Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1988). Cocaine selfadministration appears to be mediated by dopamine uptake inhibition. Prog Neuropsychopharmacol Biol Psychiatry 12: 233-239.
80. Roll JM, Higgins ST, Budney AJ, Bickel WK, Badger GJ (1996). A comparison of cocaine-dependent cigarette smokers and nonsmokers on demographic, drug use and other characteristics. Drug Alcohol Depend 40: 195-201. (Pubitemid 26131382)
81. Roll JM, Higgins ST, Tidey J (1997). Cocaine use can increase cigarette smoking: evidence from laboratory and naturalistic settings. Exp Clin Psychopharmacol 5: 263-268. (Pubitemid 27346451)
82. Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA et al (2007a). Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology 52: 985-994. (Pubitemid 46227486)
83. Rollema H, Coe JW, Chambers LK, Hurst RS, Stahl SM, Williams KE (2007b). Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation. Trends Pharmacol Sci 28: 316-325. (Pubitemid 47016686)
84. Rose JE (2007). Multiple brain pathways and receptors underlying tobacco addiction. Biochem Pharmacol 74: 1263-1270. (Pubitemid 47417938)
85. Ross JT, Corrigall WA, Heidbreder CA, LeSage MG (2007). Effects of the selective dopamine D3 receptor antagonist SB-277011A on the reinforcing effects of nicotine as measured by a progressiveratio schedule in rats. Eur J Clin Pharmacol 559: 173-179. (Pubitemid 46295412)
86. SAMSHA (ed) (2012): Substance Abuse and Mental Health Services Administration, Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-44, HHS Publication No. (SMA) 12-4713: Rockville, MD.
87. Shama G, Vijayaraghavan S (2008). Nicotinic receptors containing the a7 subunit: a model for rational drug design. Curr Med Chem 15: 2921-2932.
88. Smith JW, Mogg A, Tafi E, Peacey E, Pullar IA, Szekeres P et al (2007). Ligands selective for a4b2 but not a3b4 or a7 nicotinic receptors generalise to the nicotine discriminative stimulus in rats. Psychopharmacology 190: 157-170. (Pubitemid 46011176)
89. Spiller K, Xi XZ, Peng XQ, Newman AH, Ashby CRJ, Heidbreder C et al (2008). The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats. Psychopharmacology 196: 533-542.
90. Stolerman IP, Shoaib M (1991). The neurobiology of tobacco addiction. Trends Pharmacol Sci 12: 467-473.
91. Sziraki I, Sershen H, Benuck M, Hashim A, Laitha A (1999). Differences in receptor system participation between nicotineand cocaine-induced dopamine overflow in nucleus accumbens. NY Acad Sci 877: 800-802. (Pubitemid 29351916)
92. Tonstad S (2006). Smoking cessation efficacy and safety of varenicline, an alpha4beta2 nicotinic receptor partial agonist. J Cardiovasc Nurs 21: 433-436.
93. Watkins SS, Koob GF, Markou A (2000). Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal. Nicotine Tob Res 2: 19-37.
94. Weerts EM, Fantegrossi WE, Goodwin AK (2007). The value of nonhuman primates in drug abuse research. Exp Clin Psychopharmacol 15: 309-327. (Pubitemid 47445259)
95. Wickham R, Solecki W, Rathbun L, McIntosh JM, Addy NA (2013). Ventral tegmental area a6b2 nicotinic acetylcholine receptors modulate phasic dopamine release in the nucleus accumbens core. Psychopharmacology 229: 73-82.
96. Wouda JA, Riga D, De Vries W, Stegerman M, van Mourik Y, Schetters D et al (2011). Varenicline attenuates cue-induced relapse to alcohol, but not nicotine seeking, while reducing inhibitory response control. Psychopharmacology 216: 267-277.
97. Zernig G, O'Laughlin IA, Fibiger HC (1997). Nicotine and heroin augment cocaine-induced dopamine overflow in nucleus accumbens. Eur J Pharmacol 337: 1-10. (Pubitemid 27468854)