Behavior Genetics

, Volume 42, Issue 3, pp 423–436

Role of α7- and β4-Containing Nicotinic Acetylcholine Receptors in the Affective and Somatic Aspects of Nicotine Withdrawal: Studies in Knockout Mice

Original Research

Abstract

To assess which nicotinic acetylcholine receptors (nAChRs) are involved in the aversive aspects of nicotine withdrawal, brain reward function and the somatic signs of nicotine withdrawal were assessed in mice that lack α7 and β4 nAChR subunits. Brain reward function was assessed with the intracranial self-stimulation (ICSS) procedure, in which elevations in ICSS thresholds reflect an anhedonic mood state. At 3–6 h of spontaneous nicotine/saline withdrawal, thresholds were elevated in nicotine-withdrawing α7+/+ and β4+/+, but not α7−/− or β4−/−, mice compared with saline-withdrawing mice, indicating a delay in the onset of withdrawal in the knockout mice. From 8 to 100 h of withdrawal, thresholds in α7+/+ and α7−/− mice were equally elevated, whereas thresholds in β4+/+ and β4−/− mice returned to baseline levels. Somatic signs were attenuated in nicotine-withdrawing β4−/−, but not α7−/−, mice. Administration of a low dose of the nAChR antagonist mecamylamine induced threshold elevations in α7−/−, but not α7+/+, mice, whereas the highest dose tested only elevated thresholds in α7+/+ mice. Mecamylamine-induced threshold elevations were similar in β4−/− and β4+/+ mice. In conclusion, null mutation of the α7 and β4 nAChR subunits resulted in a delayed onset of the anhedonic aspects of the spontaneous nicotine withdrawal syndrome. Previous findings of attenuated somatic signs of nicotine withdrawal in β4−/−, but not α7−/−, mice were confirmed in the present study, indicating an important role for β4-containing nAChRs in the somatic signs of nicotine withdrawal. The mecamylamine-precipitated withdrawal data suggest that compensatory adaptations may occur in constitutive α7−/− mice or that mecamylamine may interact with other receptors besides nAChRs in these mice. In summary, the present results indicate an important role for α7 and β4-containing nAChRs in the anhedonic or somatic signs of nicotine withdrawal.

Keywords

Intracranial self-stimulation Somatic signs Reward deficit Anhedonia Mecamylamine nAChR 

References

  1. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn, text revision. American Psychiatric Press, Washington DCCrossRefGoogle Scholar
  2. Baker TB, Brandon TH, Chassin L (2004a) Motivational influences on cigarette smoking. Annu Rev Psychol 55:463–491PubMedCrossRefGoogle Scholar
  3. Baker TB, Piper ME, McCarthy DE, Majeskie MR, Fiore MC (2004b) Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev 111:33–51PubMedCrossRefGoogle Scholar
  4. Balerio GN, Aso E, Berrendero F, Murtra P, Maldonado R (2004) ∆9-tetrahydrocannabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice. Eur J Neurosci 20:2737–2748PubMedCrossRefGoogle Scholar
  5. Barik J, Wonnacott S (2006) Indirect modulation by α7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices: interaction with glutamate and GABA systems and effect of nicotine withdrawal. Mol Pharmacol 69:618–628PubMedCrossRefGoogle Scholar
  6. Cachelin AB, Jaggi R (1991) β subunits determine the time course of desensitization in rat alpha 3 neuronal nicotinic acetylcholine receptors. Pflugers Arch 419:579–582PubMedCrossRefGoogle Scholar
  7. Chavez-Noriega LE, Crona JH, Washburn MS, Urrutia A, Elliott KJ, Johnson EC (1997) Pharmacological characterization of recombinant human neuronal nicotinic acetylcholine receptors hα2β2, hα2β4, hα3β2, hα3β4, hα4β2, hα4β4 and hα7 expressed in Xenopus oocytes. J Pharmacol Exp Ther 280:346–356PubMedGoogle Scholar
  8. Clarke PBS, Schwartz RD, Paul SM, Pert CB, Pert A (1985) Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-α-bungarotoxin. J Neurosci 5:1307–1315PubMedGoogle Scholar
  9. Cordero-Erausquin M, Marubio LM, Klink R, Changeux JP (2000) Nicotinic receptor function: new perspectives from knockout mice. Trends Pharmacol Sci 21:211–217PubMedCrossRefGoogle Scholar
  10. Damaj MI, Kao W, Martin BR (2003) Characterization of spontaneous and precipitated nicotine withdrawal in the mouse. J Pharmacol Exp Ther 307:526–534PubMedCrossRefGoogle Scholar
  11. Fenster CP, Rains MF, Noerager B, Quick MW, Lester RA (1997) Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine. J Neurosci 17:5747–5759PubMedGoogle Scholar
  12. Fowler CD, Lu Q, Johnson PM, Marks MJ, Kenny PJ (2011) Habenular α5 nicotinic receptor subunit signalling controls nicotine intake. Nature 471:597–601PubMedCrossRefGoogle Scholar
  13. Franceschini D, Orr-Urtreger A, Yu W, Mackey LY, Bond RA, Armstrong D, Patrick JW, Beaudet AL, De Biasi M (2000) Altered baroreflex responses in α7 deficient mice. Behav Brain Res 113:3–10PubMedCrossRefGoogle Scholar
  14. Franceschini D, Paylor R, Broide R, Salas R, Bassetto L, Gotti C, De Biasi M (2002) Absence of α7-containing neuronal nicotinic acetylcholine receptors does not prevent nicotine-induced seizures. Brain Res Mol Brain Res 98:29–40PubMedCrossRefGoogle Scholar
  15. Frazier CJ, Rollins YD, Breese CR, Leonard S, Freedman R, Dunwiddie TV (1998) Acetylcholine activates an α-bungarotoxin-sensitive nicotinic current in rat hippocampal interneurons, but not pyramidal cells. J Neurosci 18:1187–1195PubMedGoogle Scholar
  16. Fu Y, Matta SG, Gao W, Sharp BM (2000) Local α-bungarotoxin-sensitive nicotinic receptors in the nucleus accumbens modulate nicotine-stimulated dopamine secretion in vivo. Neuroscience 101:369–375PubMedCrossRefGoogle Scholar
  17. Gerzanich V, Anand R, Lindstrom J (1994) Homomers of α8 and α7 subunits of nicotinic receptors exhibit similar channel but contrasting binding site properties. Mol Pharmacol 45:212–220PubMedGoogle Scholar
  18. Gill BM, Knapp CM, Kornetsky C (2004) The effects of cocaine on the rate independent brain stimulation reward threshold in the mouse. Pharmacol Biochem Behav 79:165–170PubMedCrossRefGoogle Scholar
  19. Gotti C, Clementi F, Fornari A, Gaimarri A, Guiducci S, Manfredi I, Moretti M, Pedrazzi P, Pucci L, Zoli M (2009) Structural and functional diversity of native brain neuronal nicotinic receptors. Biochem Pharmacol 78:703–711PubMedCrossRefGoogle Scholar
  20. Grabus SD, Martin BR, Imad Damaj M (2005) Nicotine physical dependence in the mouse: involvement of the α7 nicotinic receptor subtype. Eur J Pharmacol 515:90–93PubMedCrossRefGoogle Scholar
  21. Grady SR, Moretti M, Zoli M, Marks MJ, Zanardi A, Pucci L, Clementi F, Gotti C (2009) Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the α3β4* and α3β3β4* subtypes mediate acetylcholine release. J Neurosci 29:2272–2282PubMedCrossRefGoogle Scholar
  22. Hernandez SC, Vicini S, Xiao Y, Davila-Garcia MI, Yasuda RP, Wolfe BB, Kellar KJ (2004) The nicotinic receptor in the rat pineal gland is an α3β4 subtype. Mol Pharmacol 66:978–987PubMedCrossRefGoogle Scholar
  23. Hoyle E, Genn RF, Fernandes C, Stolerman IP (2006) Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task. Psychopharmacology (Berl) 189:211–223CrossRefGoogle Scholar
  24. Hughes JR (2007) Effects of abstinence from tobacco: etiology, animal models, epidemiology, and significance: a subjective review. Nicotine Tob Res 9:329–339PubMedCrossRefGoogle Scholar
  25. Hughes JR, Hatsukami D (1986) Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry 43:289–294PubMedCrossRefGoogle Scholar
  26. Isola R, Vogelsberg V, Wemlinger TA, Neff NH, Hadjiconstantinou M (1999) Nicotine abstinence in the mouse. Brain Res 850:189–196PubMedCrossRefGoogle Scholar
  27. Jackson KJ, Martin BR, Changeux JP, Damaj MI (2008) Differential role of nicotinic acetylcholine receptor subunits in physical and affective nicotine withdrawal signs. J Pharmacol Exp Ther 325:302–312PubMedCrossRefGoogle Scholar
  28. Johnson PM, Hollander JA, Kenny PJ (2008) Decreased brain reward function during nicotine withdrawal in C57BL6 mice: evidence from intracranial self-stimulation (ICSS) studies. Pharmacol Biochem Behav 90:409–415PubMedCrossRefGoogle Scholar
  29. Jones IW, Wonnacott S (2004) Precise localization of α7 nicotinic acetylcholine receptors on glutamatergic axon terminals in the rat ventral tegmental area. J Neurosci 24:11244–11252PubMedCrossRefGoogle Scholar
  30. Kawai H, Berg DK (2001) Nicotinic acetylcholine receptors containing α7 subunits on rat cortical neurons do not undergo long-lasting inactivation even when up-regulated by chronic nicotine exposure. J Neurochem 78:1367–1378PubMedCrossRefGoogle Scholar
  31. Kedmi M, Beaudet AL, Orr-Urtreger A (2004) Mice lacking neuronal nicotinic acetylcholine receptor βa4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures. Physiol Genomics 17:221–229PubMedCrossRefGoogle Scholar
  32. Keller JJ, Keller AB, Bowers BJ, Wehner JM (2005) Performance of α7 nicotinic receptor null mutants is impaired in appetitive learning measured in a signaled nose poke task. Behav Brain Res 162:143–152PubMedCrossRefGoogle Scholar
  33. Kenny PJ, Gasparini F, Markou A (2003) Group II metabotropic and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate glutamate receptors regulate the deficit in brain reward function associated with nicotine withdrawal in rats. J Pharmacol Exp Ther 306:1068–1076PubMedCrossRefGoogle Scholar
  34. Kenny PJ, Chartoff E, Roberto M, Carlezon WA Jr, Markou A (2009) NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala. Neuropsychopharmacology 34:266–281PubMedCrossRefGoogle Scholar
  35. Kornetsky C, Esposito RU (1979) Euphorigenic drugs: effects on the reward pathways of the brain. Fed Proc 38:2473–2476PubMedGoogle Scholar
  36. Leventhal AM, Ramsey SF, Brown RA, LaChance HR, Kahler CW (2008) Dimensions of depressive symptoms and smoking cessation. Nicotine Tob Res 10:507–517PubMedCrossRefGoogle Scholar
  37. Levin ED, Petro A, Rezvani AH, Pollard N, Christopher NC, Strauss M, Avery J, Nicholson J, Rose JE (2009) Nicotinic α7- or β2-containing receptor knockout: effects on radial-arm maze learning and long-term nicotine consumption in mice. Behav Brain Res 196:207–213PubMedCrossRefGoogle Scholar
  38. Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, Berrettini W, Knouff CW, Yuan X, Waeber G, Vollenweider P, Preisig M, Wareham NJ, Zhao JH, Loos RJ, Barroso I, Khaw KT, Grundy S, Barter P, Mahley R, Kesaniemi A, McPherson R, Vincent JB, Strauss J, Kennedy JL, Farmer A, McGuffin P, Day R, Matthews K, Bakke P, Gulsvik A, Lucae S, Ising M, Brueckl T, Horstmann S, Wichmann HE, Rawal R, Dahmen N, Lamina C, Polasek O, Zgaga L, Huffman J, Campbell S, Kooner J, Chambers JC, Burnett MS, Devaney JM, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Epstein S, Wilson JF, Wild SH, Campbell H, Vitart V, Reilly MP, Li M, Qu L, Wilensky R, Matthai W, Hakonarson HH, Rader DJ, Franke A, Wittig M, Schafer A, Uda M, Terracciano A, Xiao X, Busonero F, Scheet P, Schlessinger D, St Clair D, Rujescu D, Abecasis GR, Grabe HJ, Teumer A, Volzke H, Petersmann A, John U, Rudan I, Hayward C, Wright AF, Kolcic I, Wright BJ, Thompson JR, Balmforth AJ, Hall AS, Samani NJ, Anderson CA, Ahmad T, Mathew CG, Parkes M, Satsangi J, Caulfield M, Munroe PB, Farrall M, Dominiczak A, Worthington J, Thomson W, Eyre S, Barton A, Mooser V, Francks C, Marchini J (2010) Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet 42:436–440PubMedCrossRefGoogle Scholar
  39. Malin DH, Lake JR, Schopen CK, Kirk JW, Sailer EE, Lawless BA, Upchurch TP, SHenoi M, Rajan N (1997) Nicotine abstinence syndrome precipitated by central but not peripheral hexamethonium. Pharmacol Biochem Behav 58(3):6595–6599CrossRefGoogle Scholar
  40. Markou A, Koob GF (1992) Construct validity of a self-stimulation threshold paradigm: effects of reward and performance manipulations. Physiol Behav 51:111–119PubMedCrossRefGoogle Scholar
  41. Marks MJ, Burch JB, Collins AC (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. J Pharmacol Exp Ther 226:817–825PubMedGoogle Scholar
  42. McGehee DS, Heath MJ, Gelber S, Devay P, Role LW (1995) Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science 269:1692–1696PubMedCrossRefGoogle Scholar
  43. Meyer EL, Xiao Y, Kellar KJ (2001) Agonist regulation of rat α3β4 nicotinic acetylcholine receptors stably expressed in human embryonic kidney 293 cells. Mol Pharmacol 60:568–576PubMedGoogle Scholar
  44. Molinari EJ, Delbono O, Messi ML, Renganathan M, Arneric SP, Sullivan JP, Gopalakrishnan M (1998) Up-regulation of human α7 nicotinic receptors by chronic treatment with activator and antagonist ligands. Eur J Pharmacol 347:131–139PubMedCrossRefGoogle Scholar
  45. Naylor C, Quarta D, Fernandes C, Stolerman IP (2005) Tolerance to nicotine in mice lacking α7 nicotinic receptors. Psychopharmacology (Berl) 180:558–563CrossRefGoogle Scholar
  46. Nguyen HN, Rasmussen BA, Perry DC (2003) Subtype-selective up-regulation by chronic nicotine of high-affinity nicotinic receptors in rat brain demonstrated by receptor autoradiography. J Pharmacol Exp Ther 307:1090–1097PubMedCrossRefGoogle Scholar
  47. Olds ME, Fobes JL (1981) The central basis of motivation: intracranial self-stimulation studies. Annu Rev Psychol 32:523–574PubMedCrossRefGoogle Scholar
  48. Orr-Urtreger A, Goldner FM, Saeki M, Lorenzo I, Goldberg L, De Biasi M, Dani JA, Patrick JW, Beaudet AL (1997) Mice deficient in the α7 neuronal nicotinic acetylcholine receptor lack α-bungarotoxin binding sites and hippocampal fast nicotinic currents. J Neurosci 17:9165–9171PubMedGoogle Scholar
  49. Pakkanen JS, Jokitalo E, Tuominen RK (2005) Up-regulation of β2 and α7 subunit containing nicotinic acetylcholine receptors in mouse striatum at cellular level. Eur J Neurosci 21:2681–2691PubMedCrossRefGoogle Scholar
  50. Papke RL, Boulter J, Patrick J, Heinemann S (1989) Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. Neuron 3:589–596PubMedCrossRefGoogle Scholar
  51. Papke RL, Sanberg PR, Shytle RD (2001) Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes. J Pharmacol Exp Ther 297:646–656PubMedGoogle Scholar
  52. Parker MJ, Beck A, Luetje CW (1998) Neuronal nicotinic receptor β2 and β4 subunits confer large differences in agonist binding affinity. Mol Pharmacol 54:1132–1139PubMedGoogle Scholar
  53. Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 2nd edn. Academic Press, San DiegoGoogle Scholar
  54. Paylor R, Nguyen M, Crawley JN, Patrick J, Beaudet A, Orr-Urtreger A (1998) α7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice. Learn Mem 5:302–316PubMedGoogle Scholar
  55. Piasecki TM, Fiore MC, McCarthy DE, Baker TB (2002) Have we lost our way? The need for dynamic formulations of smoking relapse proneness. Addiction 97:1093–1108PubMedCrossRefGoogle Scholar
  56. Picciotto MR, Zoli M, Rimondini R, Lena C, Marubio LM, Pich EM, Fuxe K, Changeux JP (1998) Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine. Nature 391:173–177PubMedCrossRefGoogle Scholar
  57. Picciotto MR, Caldarone BJ, Brunzell DH, Zachariou V, Stevens TR, King SL (2001) Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications. Pharmacol Ther 92:89–108PubMedCrossRefGoogle Scholar
  58. Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, Langston JW (2000) Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J Comp Neurol 425:58–69PubMedCrossRefGoogle Scholar
  59. Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau O, Swan GE, Goate AM, Rutter J, Bertelsen S, Fox L, Fugman D, Martin NG, Montgomery GW, Wang JC, Ballinger DG, Rice JP, Bierut LJ (2007) Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet 16:36–49PubMedCrossRefGoogle Scholar
  60. Sack R, Gochberg-Sarver A, Rozovsky U, Kedmi M, Rosner S, Orr-Urtreger A (2005) Lower core body temperature and attenuated nicotine-induced hypothermic response in mice lacking the β4 neuronal nicotinic acetylcholine receptor subunit. Brain Res Bull 66:30–36PubMedCrossRefGoogle Scholar
  61. Salas R, Orr-Urtreger A, Broide RS, Beaudet A, Paylor R, De Biasi M (2003a) The nicotinic acetylcholine receptor subunit α5 mediates short-term effects of nicotine in vivo. Mol Pharmacol 63:1059–1066PubMedCrossRefGoogle Scholar
  62. Salas R, Pieri F, Fung B, Dani JA, De Biasi M (2003b) Altered anxiety-related responses in mutant mice lacking the β4 subunit of the nicotinic receptor. J Neurosci 23:6255–6263PubMedGoogle Scholar
  63. Salas R, Cook KD, Bassetto L, De Biasi M (2004a) The α3 and β4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology 47:401–407PubMedCrossRefGoogle Scholar
  64. Salas R, Pieri F, De Biasi M (2004b) Decreased signs of nicotine withdrawal in mice null for the β4 nicotinic acetylcholine receptor subunit. J Neurosci 24:10035–10039PubMedCrossRefGoogle Scholar
  65. Salas R, Main A, Gangitano D, De Biasi M (2007) Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the α7 nicotinic acetylcholine receptor subunit. Neuropharmacology 53:863–869PubMedCrossRefGoogle Scholar
  66. Salas R, Sturm R, Boulter J, De Biasi M (2009) Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice. J Neurosci 29:3014–3018PubMedCrossRefGoogle Scholar
  67. Schilstrom B, Svensson HM, Svensson TH, Nomikos GG (1998) Nicotine and food induced dopamine release in the nucleus accumbens of the rat: putative role of α7 nicotinic receptors in the ventral tegmental area. Neuroscience 85:1005–1009PubMedCrossRefGoogle Scholar
  68. Semenova S, Bespalov A, Markou A (2003) Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration. Eur J Pharmacol 472:99–110PubMedCrossRefGoogle Scholar
  69. Shiffman SM (1979) The tobacco withdrawal syndrome. NIDA Res Monogr 23:158–184PubMedGoogle Scholar
  70. Stoker AK, Markou A (2011) The intracranial self-stimulation procedure provides quantitative measures of brain reward function. In: Gould TJ (ed) Mood and anxiety related phenotypes in mice: characterization using behavioral tests, vol II (series title: Neuromethods). Humana Press, Totowa, NJ, (in press)Google Scholar
  71. Stoker AK, Semenova S, Markou A (2008) Affective and somatic aspects of spontaneous and precipitated nicotine withdrawal in C57BL/6J and BALB/cByJ mice. Neuropharmacology 54:1223–1232PubMedCrossRefGoogle Scholar
  72. Stolerman IP, Jarvis MJ (1995) The scientific case that nicotine is addictive. Psychopharmacology (Berl) 117:2–10 discussion 14–20CrossRefGoogle Scholar
  73. Stolerman IP, Chamberlain S, Bizarro L, Fernandes C, Schalkwyk L (2004) The role of nicotinic receptor α7 subunits in nicotine discrimination. Neuropharmacology 46:363–371PubMedCrossRefGoogle Scholar
  74. Tritto T, McCallum SE, Waddle SA, Hutton SR, Paylor R, Collins AC, Marks MJ (2004) Null mutant analysis of responses to nicotine: deletion of β2 nicotinic acetylcholine receptor subunit but not α7 subunit reduces sensitivity to nicotine-induced locomotor depression and hypothermia. Nicotine Tob Res 6:145–158PubMedCrossRefGoogle Scholar
  75. Walters CL, Brown S, Changeux JP, Martin B, Damaj MI (2006) The β2 but not α7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice. Psychopharmacology (Berl) 184:339–344CrossRefGoogle Scholar
  76. Wang F, Nelson ME, Kuryatov A, Olale F, Cooper J, Keyser K, Lindstrom J (1998) Chronic nicotine treatment up-regulates human α3β2 but not α3β4 acetylcholine receptors stably transfected in human embryonic kidney cells. J Biol Chem 273:28721–28732PubMedCrossRefGoogle Scholar
  77. Watkins SS, Stinus L, Koob GF, Markou A (2000) Reward and somatic changes during precipitated nicotine withdrawal in rats: centrally and peripherally mediated effects. J Pharmacol Exp Ther 292:1053–1064PubMedGoogle Scholar
  78. Wehner JM, Keller JJ, Keller AB, Picciotto MR, Paylor R, Booker TK, Beaudet A, Heinemann SF, Balogh SA (2004) Role of neuronal nicotinic receptors in the effects of nicotine and ethanol on contextual fear conditioning. Neuroscience 129:11–24PubMedCrossRefGoogle Scholar
  79. Wei ZL, Xiao Y, Yuan H, Baydyuk M, Petukhov PA, Musachio JL, Kellar KJ, Kozikowski AP (2005) Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing β2 subunits. J Med Chem 48:1721–1724PubMedCrossRefGoogle Scholar
  80. Winzer-Serhan UH, Leslie FM (1997) Codistribution of nicotinic acetylcholine receptor subunit α3 and β4 mRNAs during rat brain development. J Comp Neurol 386:540–554PubMedCrossRefGoogle Scholar
  81. World Health Organization (2009) WHO report on the global tobacco epidemic. http://whqlibdoc.who.int/publications/2009/9789241563918_eng_full.pdf (Accessed 20 April 2011)
  82. Xu W, Orr-Urtreger A, Nigro F, Gelber S, Sutcliffe CB, Armstrong D, Patrick JW, Role LW, Beaudet AL, De Biasi M (1999) Multiorgan autonomic dysfunction in mice lacking the β2 and the β4 subunits of neuronal nicotinic acetylcholine receptors. J Neurosci 19:9298–9305PubMedGoogle Scholar
  83. Young JW, Finlayson K, Spratt C, Marston HM, Crawford N, Kelly JS, Sharkey J (2004) Nicotine improves sustained attention in mice: evidence for involvement of the α7 nicotinic acetylcholine receptor. Neuropsychopharmacology 29:891–900PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Astrid K. Stoker
    • 1
    • 2
  • Berend Olivier
    • 2
  • Athina Markou
    • 1
  1. 1.Department of Psychiatry, School of MedicineUniversity of California San DiegoLa JollaUSA
  2. 2.Division of Pharmacology, Utrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands

Personalised recommendations