Arzneimittelforschung 2010; 60(9): 527-543
DOI: 10.1055/s-0031-1296322
Editio Cantor Verlag Aulendorf (Germany)

Interactions of nicotine and drugs used in the treatment of mental illnesses with respect to cognitive functions

Kinga Burda
Department of Pharmacoeconomics and Social Pharmacy, University of Medical Sciences, Poznań, (Poland)
Anna Czubak
Department of Pharmacoeconomics and Social Pharmacy, University of Medical Sciences, Poznań, (Poland)
Elżbieta Nowakowska
Department of Pharmacoeconomics and Social Pharmacy, University of Medical Sciences, Poznań, (Poland)
Krzysztof Kus
Department of Pharmacoeconomics and Social Pharmacy, University of Medical Sciences, Poznań, (Poland)
Jana Metelska
Department of Pharmacoeconomics and Social Pharmacy, University of Medical Sciences, Poznań, (Poland)
Anna Nowakowska
Department of Pharmacoeconomics and Social Pharmacy, University of Medical Sciences, Poznań, (Poland)
› Author Affiliations
Further Information

Publication History

Publication Date:
03 December 2011 (online)


Cognitive disorders in the course of mental illnesses are one of the most important and most difficult therapeutic problems related to those illnesses and the regard attention, memory, learning and sensory modulation. The limited number of nicotinic receptors (subtype 7 and α4β2) seems to cause the incidence and exacerbation of cognitive deficits in such patients. In patients with schizophrenia, the impairment of cognitive processes i also a side-effect of neuroleptics. The characteristics and intensity of the negative effect of antipsychotics on cognitive functions depends on the pharmacological action of those drugs and on the effect on dopamine and serotoninergic receptors in particular.

Cognitive function deficits observed in various mental illnesses can be modified with the use of nicotine. A cholinergic neurotransmission system is a common transmission system in the central nervous system. The effect of nicotine on other neurotransmission systems – the dopaminergic and glutaminergic system – seems to be significant for their efficacious cognitive effects in combination with antipsychotic drugs. Nicotine ma also alleviate symptoms of depression, a it amplifies serotoninergic and noradren-ergic neuronal activity.

When studies on treating cognitive disorders with nicotine are carried out, nicotine’s interactions with other drug used in therapy of those disorders must be taken into account as well as the effect of this substance on neurotransmission systems.

  • Reference

  • 1 Addington J. Group treatment for smoking cessation among persons with schizophrenia. Psychiatric Services. 1998; 49 (7) 925-8
  • 2 Addy N, Levin ED. Nicotine interactions with haloperidol, clozapine and risperidone and working memory function in rats. Neuropsychopharmacology. 2002; 27 (4) 534-41
  • 3 Adler LE, Hoffer LD, Wiser A, Freedman R. Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry. 1993; 150 (12) 1856-61
  • 4 Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K et al Schizophrenia, sensory gating and nicotinic receptors. Schizophr Bull. 1998; 24 (2) 189-202
  • 5 Aguilar MC, Gurpegui M, Diaz FJ, deLeon J. Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions. Br J Psychiatry. 2005; 86: 215-21
  • 6 Anandatheerthavrada HK, Williams JF, Wecker L. Differ ential effect of chronic nicotine administration in brain cytochrome P450 1A1–2 and P450 2E1. Biochem Biophys Commun. 1993; 194: 312-8
  • 7 Anandatheerthavrada HK, Williams JF, Wecker L. The chronic administration of nicotine induces cytochrom P450 in rat brain. J Neurochem. 1993; 60: 1941-4
  • 8 Andreasen JT, Nielsen EO, Redrobe JP. Chronic oral nicotine increases brain [3H] epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test. Psychopharmacology (Berl). 2009; 205 (3) 517-28
  • 9 Andreasen JT, Redrobe JP. Antidepressant-like effects of nicotine and mecamylamine in the mouse forced swim and tail suspension tests: role of strain, test and sex. Behav Pharmacol. 2009; 20 (3) 286-95
  • 10 Arendash GW, Sengstock GJ, Sanberg PR, Kem WR. Improved learning and memory in aged rats with chronic administration of the nicotinic receptor agonist GTS-21. Brain Res. 1995; 674 (2) 252-9
  • 11 Avila MT, Sherr JD, Hong E, Myers CS, Thaker GK. Effects of nicotine on leading saccades during smooth pursuit eye movements in smokers and nonsmokers with schizophrenia. Neuropsychopharmacology. 2003; 28 (12) 2184-2191
  • 12 Benwell ME, Balfour DJ. Regional variation in the effects of nicotine on catecholamine overflow in rat brain. Eur J Pharmacol. 1997; 325: 13-20
  • 13 Blier P, Montigny C, Chaput Y. Modifications of the serotonin system by antidepressant treatments: implications for the therapeutic response in major depression. J Clin Psychopharmacol. 1987; 7: 24-35
  • 14 Blier P, Montigny C. Possible serotoninergic mechanisms underlying the antidepressant and anti-obsessive disorder responses. Biol Psychiatry. 1998; 44: 313-23
  • 15 Borsini F, Meli A. Is the forced swimming test a suitable model for revealing antidepressant activity?. Psychopharmacology. 1988; 94: 147-60
  • 16 Breslau N, Peterson EL, Schultz LR, Chilcoat HD, Andreski P. Major depression and stages of smoking: a longitudinal investigation. Arch Gen Psychiatry. 1998; 55: 161-6
  • 17 Brockel BJ, Fowler SC. Effects of chronic haloperidol on reaction time and errors in a sustained attention task : partial reversal by anticholinergics and by amphetamine. J Pharmacol Exp Ther. 1995; 275: 1090-8
  • 18 Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM. Olanza-pine: pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet. 1999; 37: 177-93
  • 19 Chetty M, Miller R, Moodley SV. Smoking and boody weight influence the clearance of chlorpromazine. Eur J Clin Pharmacol. 1994; 46: 523-6
  • 20 Cilia J, Cluderay JE, Robbins MJ, Reavill C, Southam E, Kew JN et al Reversal of isolation-rearing-induced PPI deficits by an alpha7 nicotinic receptor agonist. Psycho pharmacology. 2005; 182 (2) 214-9
  • 21 Coney AH. Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hy-drocarbons. Cancer Res. 1982; 42: 4875-917
  • 22 Covey LS. Tobbaco cessation among patients with depression. Primary Care. 1999; 26: 691-706
  • 23 Czubak A, Nowakowska E, Golembiowska K, Kus K, Burda K, Metelska J. Effect of venlafaxine and nicotine on the level of neurotransmitters and their metabolites in rat brains. J Physiol Pharmacol Forthcoming 2010.
  • 24 Czubak A, Nowakowska E, Kus K, Matschay A, Kokot Z. The effects of nicotine and mecamylamine on spatial memory in rats. 20th ECNP Congress, 13–17 October 2007 Vienna, Austria. Eur Neuropsychopharmacol. 2007; 17 (4) 253-4 Poster
  • 25 Dalack GW, Healy DJ, Meador-Woodruff JH. Nicotine dependence in schizophrenia: clinical phenomena and lab oratory findings. Am J Psychiatry. 1998; 155 (11) 1490-501
  • 26 DeLeon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res. 2005; 76 (2–3) 135-57
  • 27 DeLuca V, Wang H, Squassina A, Wong GW, Yeomans J, Kennedy JL. Linkage of M5 muscarinic and alphα 7 nicotinic receptor genes on 15q13 to schizophrenia. Neuropsychobiology. 2004; 50 (2) 124-7
  • 28 DeLuca V, Wong AH, Muller DJ, Wong GW, Tyndale RF, Kennedy JL. Evidence of association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenia patients. Neuropsychopharmacology. 2004; 29 (8) 1522-6
  • 29 Detke MJ, Johnson J, Lucki I. Acute and chronic antide-pressant drug treatment in the rat forced swimming test model of depression. Exp Clin Psychopharmacol. 1997; 5 (2) 107-12
  • 30 Detke MJ, Rickels M, Lucki I. Active behaviors in the rat forced swimming test differentially produced by serotoni-nergic and noradrenergic antidepressants. Psychopharmacolog. 1995; 121: 66-72
  • 31 Dettling M, Sachse C, Brockmöller J, Schley J, Müller-Oerlinghausen B, Pickersgill I et al Long-term therapeutic drug monitoring of clozapine and metabolites in psychiatric in- and outpatients. Psychopharmacol. 2000; 152: 80-86
  • 32 Deutsch SI, Rosse RB, Schwartz BL, Weizman A, Chilton M, Arnold DS et al Therapeutic implications of a selective alpha7 nicotinic receptor abnormality in schizophrenia. Isr J Psychiatry Relat Sci. 2005; 42 (1) 33-44
  • 33 Didriksen M. Effects of antipsychotics on cognitive behaviour in rats using the delayed non-match to position para digm. Eur J Pharmacol. 1995; 281 (3) 241-50
  • 34 Djuri’c VJ, Dunn E, Overstreet DH, Dragomir A, Steiner M. Antidepressant effect of ingested nicotine in female rats of Flinders resistant and sensitive lines. Physiol Behav. 1999; 67: 533-7
  • 35 Drew AE, Werling LL. Nicotinic receptor-mediated regula-tion if the dopamine transporter in rat prefrontocortical slices following chronic in vivo administration of nicotine. Schizophr Res. 2003; 65 (1) 47-55
  • 36 Durany N, Zochling R, Boissl KW, Paulus W, Ransmayr G, Tatschner T et al Human post-mortem striatal alpha4-beta2 nicotinic acetylocholine receptor density in schizophrenia and Parkinson’s syndrome. Neurosci Lett. 2000; 287 (2) 109-12
  • 37 Eaton DL, Gallagher EP, Bammler TK, Kunze KL. Role of cytochrome P4501A2 in chemical carcinogenesis: Implications for human variability in expression and enzyme activity. Pharmacogenetics. 1995; 5: 259-74
  • 38 Ellison GD, Johansson P, Levin ED, See RE, Gunne L. Chronic neuroleptics alter the effects of the D1 agonist SK&F 38393 and the D2 agonist LY 171555 on oral movements in rats. Psychopharmacology. 1988; 96: 253-57
  • 39 Engberg G, Erhardt S, Sharp T, Hajos M. Nicotine inhibits firing activity of dorsal raphe’ 5-HT neurones in vivo. Naunyn-Schmiedeberg’s Arch Pharmacol. 2000; 362: 41-5
  • 40 Ereshefsky L, Jann MW, Saklad SR, Davis CM, Richards AL, Burch NR. Effect of smoking on fluphenazine clear ance in psychiatric patients. Biol Psychiatry. 1985; 20: 329-52
  • 41 Ereshefsky L, Sakald SR, Watanambe MD, Davis CM, Jann MW. Thiotixene pharmatocinetic interaction: a study of hepatic enzyme inducers, clearance inhibitors and demographic variables. J Clin Pharmacol. 1991; 11: 296-301
  • 42 Ferguson SM, Brodkin JD, Lloyd GK, Menzaghi F. Antide-pressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression. Psychopharmacology. 2000; 152: 295-303
  • 43 Florek E, Piekoszewski W. Interakcje leków z dymem tytoniowym. Katedra i Zaklad Toksykologii AM im. K. Marcin-kowskiego. Poznan: Sowa-Druk; 2006. Polish.
  • 44 Freedman R, Adams CE, Leonard S. The alpha7-nicotinic acetylocholine receptor and the pathology of hippocam-pal interneurons in schizophrenia. J Chem Neuroanat. 2000; 20 (3–4) 299-306
  • 45 Freedman R, Hall M, Adler LE, Leonard S. Evidence in postmortem brain tissue for decreased numbers of hippo-campal nicotinic receptors in schizophrenia. Biol Psychiatry. 1995; 38 (1) 22-33
  • 46 Fulton B, Goa KL. Olanzapine: a review of its pharma-cological properties and therapeutic efficacy in the management of schizophrenia and related psychoses. Drugs. 1997; 53: 281-98
  • 47 George TP, Vessicchio JC, Termine A, Sahady DM, Head CA, Pepper WT et al Effects of smoking abstinence on vi-suospatial working memory function in schizophrenia. Neuropsychopharmacolog. 2002; 26 (1) 75-85
  • 48 Gerstenberg G, Aoshima T, Fukasawa T, Yoshida K, Takahashi H, Higuchi H et al Effects of the CYP 2D6 genotype and cigarette smoking on the steady-state plasma concentrations of fluvoxamine and its major metabolite flu voxamino acid in Japanese depressed patients. Ther Drug Monit. 2003; 25: 463-8
  • 49 Gex-Fabry M, Balant-Georgia AE, Balant LP. Clopramine metabolism model-based analysis in variability factors from drug monitoring data. Clin Pharmacokinet. 1990; 19: 241-55
  • 50 Geyer MA, Tamminga CA. Measurement and treatment research to improve cognition in schizophrenia: neurophar-macological aspects. Psychopharmacology. 2004; 174 (1) 54-6
  • 51 Gilbert DG. Depression, smoking, and nicotine: toward a bioinformational situation by trait model. Drug Dev Res. 1996; 38: 267-77
  • 52 Glassman AH. Cigarette smoking: implications for psychiatric illness. Am J Psychiatry. 1993; 150: 546-53
  • 53 Goff DC, Henderson DC, Amico E. Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am J Psych. 1992; 149: 1189-94
  • 54 Goldberg TE, Weinberger DR. Effects of neuroleptic medications on the cognition of patients with schizophrenia: a review of recent studies. J Clin Psychiatry. 1996; 57 (01) 62-5
  • 55 Goldberg TE, Weinberger DR. The effects of clozapine on neurocognition: an overview. J Clin Psychiatry. 1994; 55 (B) 88-90
  • 56 Green A, Ellis KA, Ellis J, Bartholomeusz CF, Ilic S, Croft RJ et al Muscarinic and nicotinic receptor modulation of object and spatial n-back working memory in human. Pharmacol Biochem Behav. 2005; 81 (3) 575-84
  • 57 Green MF, Marshall BD, Wirshing WC, Ames D, Marder SR, McGurk S et al Does risperidone improve verbal working memory in treatment-resistant schizophrenia?. Am J Psychiatry. 1997; 154 (6) 799-804
  • 58 Grenhoff J, Aston-Jones G, Svensson TH. Nicotinic effects on the firing pattern of midbrain dopamine neurons. Act Physiol Scand. 1986; 128: 151-8
  • 59 Guan ZZ, Zhang X, Blennow K, Nordberg A. Decreased protein level of nicotinic receptor alpha7 subunit in the frontal cortex from schizophrenic brain. Neuroreport. 1999; 10 (8) 1779-82
  • 60 Hagger C, Buckley P, Kenny JT, Friedman L, Ubogy D, Meltzer HY. Improvement in cognitive functions and psy-chiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol Psychiatry. 1993; 34 (10) 702-12
  • 61 Hahn B, Sharples CG, Wonnacott S, Shoaib M, Stolerman IP. Attentional effects of nicotinic agonists in rats. Neuropharmacology. 2003; 44 (8) 1054-67
  • 62 Hajos M, Hurst RS, Hoffmann WE, Krause M, Wall TM, Higdon NR et al The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-azabicyclo [2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats. J Pharmacol Exp Ther. 2005; 312 (3) 1213-22
  • 63 Haring C, Fleischhacker WW, Schett P et al Influence of patient-related variables on clozapine plasma levels. Am Psychiatry. 1990; 147: 1471-5
  • 64 Haring C, Meise U, Humpel C et al Dose-related plasma levels of clozapine: Influence of smoking behaviour, sex and age. Psychopharmacol. 1989; 99: 38-40
  • 65 Harris J, Kongs S, Allensworth D, Martin L, Tregallas J, Sullivan B et al Effects of nicotine on cognitive deficits in schizophrenia. Neuropsychopharmacolog. 2004; 29 (7) 1378-85
  • 66 Hertel P, Nomikos GG, Iurlo M, Svensson TH. Risperi-done: regional effects in vivo on release and metabolism of dopamine and serotonin in the rat brain. Psychopharmacology. 1996; 124: 74-86
  • 67 Hoff AL, Faustman WO, Wieneke M, Espinoza S, Costa M, Wolkowitz O et al The effects of clozapine on symptom reduction, neurocognitive function, and clinical manage ment in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology. 1996; 15 (4) 361-9
  • 68 Hughes JR, Hatsukami DK, Mitchell JE et al Prevalence of smoking among psychiatric outpatients. Am J Psych. 1986; 143: 993-7
  • 69 Hughes JR. Possible effects of smoke-free inpatient units on psychiatric diagnosis and treatment. J Clin Psychiatry. 1993; 54 (3) 109-14
  • 70 Inami R, Kirino E, Inoue R, Arai H. Transdermal nicotine administration enhances automatic auditory processing reflected by mismatch negativity. Pharmacol Biochem Behav. 2005; 80 (3) 453-61
  • 71 Ishida M, Otani K, Kaneko S. Effect of various factors on steady state plasma concentration of trazodone and its active metabolite m-chlorphenylpiperazine. Int Clin Psychopharmacol. 1995; 10: 143-6
  • 72 Jacobsen LK, D’Souza DC, Mencl WE, Pugh KR, Skudlarski P, Krystal JH. Nicotine effects on brain function and functional connectivity in schizophrenia. Biol Psychiatry. 2004; 55 (8) 850-8
  • 73 Jann MW, Saklad SR, Ereshefsky L et al Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance. Psychopharmacolog. 1986; 90: 468-70
  • 74 John VA, Luscombe DK, Kemp H. Effect of age, cigarette smoking and the oral contraceptive an the pharmacoki-netics clomipramine and its desmethyl aetabolite during chronic dosing. J Int Med Res. 1980; 8 (3) 88-95
  • 75 Kelly JP, Leonard BE. The effect of tianepine and sertra-line in three animals models of depression. Neuropharmacology. 1994; 33: 1101-6
  • 76 Kendler KS, Neale MC, MacLean CJ, Heath AC, Eaves LJ, Kessler R. Smoking and major depression: a casual analy-sis. Arch Gen Psychiatry. 1993; 50: 36-43
  • 77 Kennedy SH, Evans KR, Kruger S, Mayberg HS, Meyer JH, McCann S et al Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry. 2001; 158 (6) 899-905
  • 78 Kenny PJ, File SE, Rattray M. Nicotine regulates 5-HT1A receptor gene expression in the cerebral cortex and dorsal hippocampus. Eur J Neurosci. 2001; 13: 1267-71
  • 79 Kisicki JC, Bergstorm RF, Cerimele BJ. Olanzapine: bio-equivalence of capsule and tablets formulations. Chicago (USA):: Lilly Laboratory of Clinical Research. Eli Lilly and Co.; 995
  • 80 Koike K, Hashimoto K, Takai N, Shimizu E, Komatsu N, Watanabe H et al Tropisetron improves deficits in auditory P50 suppression in schizophrenia. Schizophr Res. 2005; 76 (1) 67-72
  • 81 Kreiss DS, Lucki I. Effects of acute and repeated administration of antidepressant drugs on extracellular levels of 5-hydroxytryptamine measured in vivo. J Pharmacol Exp Ther. 1995; 274: 866-76
  • 82 Lambe EK, Picciotto MR, Aghajanian GK. Nicotine induces glutamate release from thalamocortical terminals in pre-frontal cortex. Neuropsychopharmacology. 2003; 28 (2) 216-25
  • 83 Larrison-Faucher AL, Matorin AA, Sereno AB. Nicotine reduces antisaccade errors in task impaired schizophrenic subjects. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28 (3) 505-16
  • 84 Lee MA, Jayathilake K, Meltzer HY. A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic-responsive schizophrenia. Schizophr Res. 1999; 37 (1) 1-11
  • 85 Leonard S, Breese C, Adams C, Benhammou K, Gault J, Stevens K et al Smoking and schizophrenia receptor expression. Eur J Pharmacol. 2000; 393 (1–3) 237-42 [special issue]
  • 86 Leonard S, Gault J, Hopkins J, Logel J, Vianzon R, Short M et al Association of promoter variants in the alphα7 nico-tinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Arch Gen Psychiatry. 2002; 59 (12) 1085-96
  • 87 Lerman C, Audrian J, Orleans CT, Boyd R, Gold K, Main D et al Investigation of mechanisms linking depressed mood to nicotine dependence. Addict Behav. 1996; 21: 9-19
  • 88 Levin E, Christopher N. Lobeline-induced learning improvements in rats in the radial-arm maze. Pharmacol Biochem Behav. 2003; 76: 133-99
  • 89 Levin E, Christopher N. Persistence of nicotinic agonist RJR2403 induced working memory improvement in rats. Drug Dev Res. 2002; 55: 97-103
  • 90 Levin E, Icenogle L, Farzad A. Ketanserin attenuates nicotine-induced working memory improvement in rats. Pharmacol Biochem Behav. 2005; 82 (2) 289-92
  • 91 Levin ED, Bettegowda C, Blosser J, Gordon J. AR-R17779, and alpha7 nicotinic agonist, improves learning and memory in rats. Behav Pharmacol. 1999; 10 (6–7) 675-80
  • 92 Levin ED, Bettegowda C, Weaver T, Christopher NC. Nico-tine-dizocilpine interactions and working and reference memory performance of rats in the radial-arm maze. Pharmacol Biochem Behav. 1998; 61 (3) 335-40
  • 93 Levin ED, Galen DM, Ellison GD. Chronic haloperidol effects on oral movements and radial-arm maze perfor-mance in rats. Pharmacol Biochem Behav. 1987; 26 (1) 1-6
  • 94 Levin ED, McClernon FJ, Rezvani AH. Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification and anatomic localization. Psychopharmacolog. 2006; 184: 523-39
  • 95 Levin ED, Petro A, Beatty A. Olanzapine interactions with nicotine and mecamylamine in rats: effects on memory function. Neurotoxicol Teratol. 2005; 27 (3) 459-64
  • 96 Levin ED, Rezvani AH. Development of nicotinic drug therapy for cognitive disorders. Eur J Pharmacol. 2000; 393 (1–3) 141-6
  • 97 Levin ED, Rezvani AH. Nicotinic interactions with anti-psychotic drugs, models of schizophrenia and impacts on cognitive function. Biochem Pharmacol. 2007; 74: 1182-91
  • 98 Levin ED, Wilson W, Rose JE, McEvoy J. Nicotine – haloperidol interactions and cognitive performance in schizophrenics. Neuropsychopharmacolog. 1996; 15 (5) 429-36
  • 99 Levin ED. Chronic haloperidol administration does not block acute nicotine-induced improvements in radial-arm maze performance in the rat. Pharmacol Biochem Behav. 1997; 58 (4) 899-902
  • 100 Leysen JE, Gommeren W, Eens A, de Chaffoy de Courcelles D, Stoof JC et al Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther. 1998; 247: 661-70
  • 101 Li Q, Muma NA, vandeKar LD. Chronic fluoxetine induces a gradual desensitization of 5-HT1A receptors: reductions in hypothalamic and midbrain Gi and G(o) proteins and in neuroendocrine responses to a 5-HT1a agonist. J Pharmacol Exp Ther. 1996; 279: 1035-42
  • 102 Lieberman J, Mailman R, Duncan G, Sikich L, Chakos M, Nichols D et al Serotonergic basis of antipsychotic drug effects in schizophrenia. Biol Psychiatry. 1998; 44: 1099-117
  • 103 Linnoila M, George L, Guthrie S et al Effect of alcohol consumption and cigarette smoking on antidepressant levels of depressed patients. Am J Psych. 1981; 138: 841-2
  • 104 Lucas D, Menéz C, Girre C et al Cytochrome P450 2E genotype and chlorzoxazone metabolism in healthy and alcoholics. Caucasian subjects. Pharmacogenetics. 1995; 5: 298-304
  • 105 Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol. 1997; 8: 523-32
  • 106 Markou A, Kosten TR, Koob GF. Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacolog. 1998; 18: 135-74
  • 107 Martínez-González D, Prospéro-García O, Mihailescu S, Drucker-Colín R. Effects of nicotine on alcohol intake in a rat model of depression. Pharmacol Biochem Behav. 2002; 72: 355-64
  • 108 Martin LF, Kem WR, Friedman R. Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology. 2004; 174 (1) 54-64
  • 109 Mastropaolo J, Rosse RB, Deutsch SI. Anabasine, a selective nicotinic acetylcholine receptor agonist, antagonize MK-80-elicited mouse popping behavior, an animal model of schizophrenia. Behav Brain Res. 2004; 153 (2) 419-22
  • 110 Matsubara S, Matsubara R, Kusumi I, Koyama T, Yamashita I. Dopamine D1, D2 and serotonin2 receptor occupation by typical and atypical antipsychotic drugs in vivo. J Pharmacol Exp Ther. 1993; 265: 498-508
  • 111 Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S et al Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry. 2000; 48 (8) 830-43
  • 112 McCarthy RH. Seizures following smoking cessation in a clozapine responder. Pharmacopsychiatry. 1994; 27: 210-1
  • 113 McEvoy J, Freudenreich O, Levin E, Rose J. Haloperidol increases smoking in patients with schizophrenia. Psychopharmacolog. 1995; 119: 124-6
  • 114 McEvoy J, Freudenreich O, McGee M, Vanderzwaag C, Levin E, Rose J. Clozapine decreases smoking in patients with chronic schizophrenia. Biol Psychiatry. 1995; 37 (8) 550-2
  • 115 McEvoy JP, Freudenreich O, Wilson WH. Smoking and therapeutic response of clorazepine in patients with schizophrenia. Biol Psychiatry. 1999; 46: 125-9
  • 116 McGaughy J, Kaiser T, Sarter M. Behavioral vigilance following infusions of 192 IgG-Sapoin into the basal for brain: selectivity of the behavioral impairment and rela-tion to cortical ACh-positive fiber density. Behavioral Neuroscience. 1996; 110: 247-65
  • 117 McGehee DS, Heath MJS, Gelber S, Devay P, Role LW. Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science. 1995; 269 (5231) 1692-6
  • 118 McGurk S, Levin ED, Butcher LL. Cholinergic-dopaminer gic interactions in radial-arm maze performance. Behav Neural Biol. 1988; 49: 234-9
  • 119 McGurk SR. The effects of clozapine on cognitive functioning in schizophrenia. J Clin Psychiatry. 1999; 60 (12) 24-9
  • 120 Meltzer HY, McGurk SR. The effects of clozapine, risperi-done, and olanzapine on cognitive function in schizophrenia. Schizophr Bull. 1999; 25 (2) 233-55
  • 121 Meltzer HY, Thompson PA, Lee MA, Ranjan R. Neuropsychologic deficits in schizophrenia: relation to social function and effect of antipsychotic drug treatment. Neuropsychopharmacology. 1996; 14 (03) 27-33
  • 122 Meyer UA. Overview of enzyme of drug metabolism. J Pharmacokinet Biopharm. 1996; 24: 449-59
  • 123 Midha KK, Chakraborty BS, Ganes DA. Intersubject variation in the pharmacokinetics of haloperidol and reduced haloperidol. J Clin Psychopharmacol. 1989; 9: 98-104
  • 124 Mihailescu S, Palomero-Rivero M, Meade-Huerta P, Maza-Flores A, Drucker-Colín R. Effects of nicotine and mecamylamine on rat dorsal raphe neurons. Eur J Pharmacol. 1998; 360: 31-6
  • 125 Miller DD, Kelly MW, Perry PJ et al The influence of cigarette smoking on haloperidol pharmacokinetics. Biol Psychitary. 1990; 28: 529-31
  • 126 Mortimer AM. Cognitive function in schizophrenia – do neuroleptics make a difference?. Pharmacol Biochem Behav. 1997; 56 (4) 789-95
  • 127 Mumenthaler MS, Yesavage JA, Taylor JL, O’Hara R, Friedman L, Lee H et al Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects. Neuropsychopharmacology. 2003; 28 (7) 1366-73
  • 128 Murphy BL, Roth RH, Arnsten AF. Clozapine reverses the spatial working memory deficits induced by FG7142 in monkeys. Neuropsychopharmacology. 1997; 16 (6) 433-7
  • 129 Myers CS, Robles O, Kakoyannis AN, Sherr JD, Avila MT, Blaxton TA et al Nicotine improves delayed recognition in schizophrenic patients. Psychopharmacology. 2004; 174 (3) 334-340
  • 130 Newhouse P, Singh A, Potter A. Nicotine and nicotinic receptor involvement in neuropsychiatric disorders. Curr Top Med Chem. 2004; 4 (3) 267-82
  • 131 Newhouse PA, Potter A, Levin ED. Nicotinic system involvement in Alzheimer’s and Parkinson’s diseases: implications for therapeutics. Drug Aging. 1997; 11 (3) 206-28
  • 132 Nieoullon A. Dopamine and the regulation of cognition and attention. Prog Neurobiol. 2002; 67: 53-83
  • 133 Nowakowska E, Chodera A, Kus K, Rybakowski J, Kucma A. eds. Comparison of risperidone and haloperidol in an-xiolytic, antidepressant and cognitive functions tests in rats. Georg-August-Universität; 1999 March 01; Göttingen, German Journal of Psychiatry. 1999
  • 134 Nowakowska E, Chodera A. Kus. Influence of olanzapine on cognitive functions and catalepsy in rats after single and chronic administration. Pol J Pharmacol. 1999; 51: 295-300
  • 135 Nowakowska E, Kus K, Chodera A. Comparison of behavioural effects of venlafaxine and imipramine in rats. Arzneimittelforschung. 2003; 53 (4) 237-42
  • 136 Nowakowska E, Kus K, Florek E, Czubak A, Jodynis-Liebert J, Hertmanowska H. The influence of tobacco smoke and nicotine on antidepressant and memory improving effects of venlafaxine. Hum Exp Toxicol. 2006; 25 (4) 199-209
  • 137 Nowakowska E, Kus K, Glowacka D, Krzyzanski W. eds. The influence of clozapine on cognitive functions and catalepsy in rats after single and chronic administration. 18th ECNP Congress 2005 Sep 22–26; Amsterdam, Holland. Eur Neuropsychopharmacol. 2005
  • 138 Nowakowska E, Kus K, Krzyzanski W, Czubak A. Influence of haloperidol and clozapine on some behavioral effects in rats. Arzneimittelforschung. 2006; 56 (12) 807-13
  • 139 O’Neill HC, Rieger K, Kem WR, Stevens KE. DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared rats. Psychopharmacology. 2003; 169 (3–4) 332-9
  • 140 Oades R, Rao M, Bender S, Sartory G, Muller B. Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor. Behav Pharmacol. 2000; 11: 7-23
  • 141 Page ME, Detke MJ, Dalvi A, Kirby LG, Lucki I. Serotonergic mediation of the effects of fluoxetine, but not desipra-mine, in the rat forced swimming test. Psychopharmacology (Berl). 1999; 147 (2) 162-7
  • 142 Pan L, Stichele RV, Posseel M, Berlo A, DeSchepper N, Belpaire FM. Effect of smoking, CYP 2D6 genotype, and concomitant drug intake on the steady state plasma concentrations of haloperidol and reduced haloperidol in schizophrenic inpatients. Ther Drug Metabol. 1999; 21: 489-97
  • 143 Pantuck EJ, Pantuck CE, Andersen EK, Coney AH, Kappas A. Cigarette smoking and chlorpromazine disposition and action. Clin Pharmacol Ther. 1982; 31: 533-8
  • 144 Perel JM, Hurwic MJ, Kanzler MB. Pharmacodynamics of imipramine in depressed patients. Psychopharmacol Bull. 1975; 11: 16-8
  • 145 Perel JM, Mendlewicz J, Shostak M. Plasma levels of imipramine in depression. Environmental and genetic factors. Neuropsychobiology. 1976; 2: 193-202
  • 146 Perez-Gomez M, Junque C. Clozapina: estudios neuropsicologicos y de resonancia magnetica. Actas Esp Psiquiatr. 1999; 27 (5) 341-6 Spanish
  • 147 Perry PJ, Browne JL, Prince RA et al Effects of smoking on nortriptyline plasma concentrations in depressed patients. Ther Drug Monit. 1986; 8: 279-84
  • 148 Perry PJ, Miller DD, Arndt SV. Haloperidol dosing requirements: The contribution of smoking and nonlinear phar-macokinetics. J Clin Psychopharmacol. 1993; 13: 46-51
  • 149 Philip NS, Carpenter LL, Tyrka AR, Whiteley LB, Price LH. Varenicline augmentation in depressed smokers: an 8- week, open-label study. J Clin Psychiatry. 2009; 70 (7) 1026-31
  • 150 Picciotto MR, Caldarone BJ, King SL, Zachariou V. Nicotinic receptors in the brain: links between molecular biology and behavior. Neuropsychopharmacology. 2002; 22 (5) 451-65
  • 151 Popik P, Kozela E, Krawczyk M. Nicotine and nicotinic recetor antagonists potentiate the antidepressant-like of imipramine and citalopram. Br J Pharmacol. 2003; 139 (6) 1196-202
  • 152 Porsolt R, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatment. Nature. 1977; 266: 730-2
  • 153 Porsolt RD, Anton G, Deniel M, Jalfre M. Behavioral despair in rats: a new model sensitive to antidepressant treat ments. Eur J Pharmacol. 1978; 47: 379-91
  • 154 Quattrocki E, Baird A, Yurgelun-Todd D. Bilogical aspects if the link between smoking and depression. Biol Psychiatry. 2000; 8: 99-110
  • 155 Raap DK, Evans S, Garcia F, Li Q, Muma NA, Wolf WA et al Daily injections of fluoxetine induce dose-dependent desensitization of hypothalamic 5-HT1A receptors reductions in neuroendocrine responses to 8-OH-DPAT and in levels of Gz and Gi proteins. J Pharmacol Exp Ther. 1999; 288: 98-106
  • 156 Rezvani A, Levin E. Nicotine interactions with the NMDA glutaminergic antagonist dizocilpine and attentional function. Eur J Pharmacol. 2003; 465: 83-90
  • 157 Rezvani AH, Caldwell DP, Levin ED. Chronic nicotine interactions with clozapine and risperidone and attentional function in rats Prog Neuropsychopharmacol. Biol Psychiatry. 2006; 30 (2) 190-7
  • 158 Rezvani AH, Caldwell DP, Levin ED. Nicotine-serotonergic drug interactions and attentional performance in rats. Psychopharmacology. 2005; 179: 521-8
  • 159 Rezvani AH, Kholdebarin E, Dawson E, Levin ED. Nicotine and clozapine effects on attentional performance impaired by the NMDA antagonist dizocilpine in female rats. Int J Neuropsychopharmacol. 2008; 11 (1) 63-70
  • 160 Rezvani AH, Levin ED. Cognitive effects of nicotine. Biol Psychiatry. 2001; 49: 258-67
  • 161 Rezvani AH, Levin ED. Nicotine–antipsychotic drug inter actions and attentional performance in female rats. Eur Pharmacol. 2004; 486: 175-82
  • 162 Rigal JG, Albin H, Cuchier AR. Imipramine blood level and clinical outcome. J Clin Psychopharmacol. 1987; 7: 222-9
  • 163 Ripoll N, Bronnec M, Bourin M. Nicotinic receptors and schizophrenia. Curr Med Res Opin. 2004; 20 (7) 1057-74
  • 164 Roberts DL. Natural tobacco flavor. Rec Adv Tobacco. 1988; 14: 45-81
  • 165 Rutter JJ, Gundlah C, Auerbach SB. Increase in extracellular serotonin produced by uptake inhibitors is enhanced after chronic treatment with fluoxetine. Neurosci Lett. 1994; 171: 183-6
  • 166 Sacco KA, Bannon KL, George TP. Nicotinic receptor mech-anisms and cognition in normal states and neuropsychi-atric disorders. J Psychopharmacol. 2004; 18 (4) 457-74
  • 167 Sacco KA, Termine A, Seyal A, Dudas MM, Vessicchio JC, Krishnan-Sarin S et al Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry. 2005; 62 (6) 649-59
  • 168 Salin-Pascual RJ, de la Fuente JR, Garci’a Polo L, Drucker-Colin R. Effects of transdermal nicotine on mood and sleep in nonsmoking major depressed patients. Psychopharmacology. 1995; 121: 476-9
  • 169 Salin-Pascual RJ, Drucker-Colin R. A novel effect of nicotine on mood and sleep in major depression. NeuroReport. 1998; 9: 57-60
  • 170 Salokangas RK, Saarijarvi S, Taiminen T et al Effect of smoking on neuroleptics in schizophrenia. Schizophr Res. 1997; 23: 55-60
  • 171 Sarter M, Givens B, Bruno J. The cognitive neuroscience of sustained attention: where top-down meets bottom-up. Brain Res Rev. 2001; 35: 146-60
  • 172 Schotte A, Janssen P, Megens A, Leysen J. Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography. Brain Res. 1992; 631: 191-202
  • 173 Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS et al Risperidone compared wit new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology. 1996; 124: 57-73
  • 174 Schwieler L, Engberg G, Erhardt S. Clozapine modulate midbrain dopamine neuron firing via interaction wit the NMDA receptor complex. Synapse. 2004; 52 (2) 114-22
  • 175 Schwieler L, Erhardt S. Inhibotory action of clozapine on rat ventral tegmental area dopamine neurons following increased levels of endogenous kynurenic acid. Neuropsychopharmacology. 2003; 28 (10) 1770-7
  • 176 Semba J, Mataki C, Yamada S, Nankai M, Toru M. Antidepressant-like effects of chronic nicotine on learned helplessness paradigm in rats. Biol Psychiatry. 1998; 43: 389-91
  • 177 Seth P, Cheeta S, Tucci S, File SE. Nicotinic-serotoninergic interactions in brain and behavior. Pharmacol Biochem Behav. 2002; 71: 795-805
  • 178 Sharma T, Mockler D. The cognitive efficacy of atypical antipsychotics in schizophrenia. J Clin Psychopharmacol. 1998; 18 (2 suppl 1) 9-12
  • 179 Sherr JD, Myers C, Avila MT, Elliott A, Blaxton TA, Thaker GK. The effects of nicotine on specific eye tracking measures in schizophrenia. Biol Psychiatry. 2002; 52 (7) 721-8
  • 180 Shimoda K, Noguchi T, Ozeki Y. metabolism of clomipramine in a Japanese psychiatric population: hydrocylation, demethylation and glucuronidation. Neuropsychopharmacolog. 1995; 12: 323-33
  • 181 Shimoda K, Someya T, Morita S. et al. Lower plasma lev els of haloperidol in smoking than in nonsmoking schizophrenic patients Ther Drug Monitor. 1999; 21: 293-6
  • 182 Silvestri S, Negrete JC, Seeman MV, Shammi CM, Seeman P. Does nicotine affect D2 receptor upregulation? A case-control study. Acta Psychiatr Scand. 2004; 109 (4) 313-8
  • 183 Simosky JK, Stevens KE, Adler LE, Freedman R. Clozapine improves deficient inhibitory auditory processing in DBA 2 mice, via a nicotinic cholinergic mechanism. Psycho pharmacology. 2003; 165 (4) 386-96
  • 184 Singh A, Potter A, Newhouse P. Nicotinic acetylcholine receptor system and neuropsychiatric disorders. IDrugs. 2004; 7 (12) 1096-1103
  • 185 Skarsfeldt T. Differential effect of antipsychotics on place navigation of rats in the Morris water maze. A comparative study between novel and reference antipsychotics Psychopharmacology. 1996; 124 (1–2) 126-33
  • 186 Smith RC, Singh A, Infante M, Khandat A, Kloos A. Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia. Neuropsychopharmacology. 2002; 27 (3) 479-97
  • 187 Spigset O, Axelsson S, Norstrom A et al The major fluvoxamine metabolite in urine is formed by CYP2D6. Eur Clin Pharmacol. 2001; 57: 653-8
  • 188 Spigset O, Caleborg L, Hedenmalm K. Effect if cigarette smoking on fluwoxamine pharmacokinetics in human. Clin Pharmacol The. 1995; 58: 88-95
  • 189 Stassen HH, Bridler R, Hagele S, Hergersberg M, Mehmann B, Schinzel A et al Schizophrenia and smoking evidence for a common neurobiological basis. Am J Med Genet. 2000; 96 (2) 173-7
  • 190 Stevens KE, Freedman R, Collins AC, Hall M, Leonard S, Marks JM et al Genetic correlation of inhibitory gating of hippocampal auditory evoked response and alpha-bungaro-toxin-binding nicotinic cholinergic receptors in inbred mouse strains. Neuropsychopharmacolog. 1996; 15 (2) 152-62
  • 191 Stimmel GL, Fallon I. Chlorpromazine plasma level adverse effects and tobacco smoking. Case report. J Clin Psychiatry. 1983; 44: 420-2
  • 192 Stockmeier CA. Neurobiology of serotonin in depression and suicide. Ann NY Acad Sci. 1997; 836: 220-32
  • 193 Strand JE, Nyback H. Tobacco use in schizophrenia: study of cotinine concentrations in the saliva of patients and controls. Eur Psychiatry. 2005; 20 (1) 50-4
  • 194 Sumiyoshi T, Kido H, Sakamoto H, Urasaki K, Suzuki K, Yamaguchi N et al In vivo dopamine- D2 and serotonin-5-HT2 receptor binding study of risperidone and ha loperidol. Pharmacol Biochem Behav. 1994; 47: 553-7
  • 195 Sutfin TA, Perini GI, Molnar G et al Multiple-dose pharmacokinetics of imipramine and its major active and conjugated metabolites in depressed patients. J Clin Psychopharmacol. 1988; 8: 48-53
  • 196 Swett C. Drowsiness due to chlorpromazine in relation to cigarette smoking. Arch Gen Psychiatry. 1974; 31: 211-3
  • 197 Tatsumi R, Fujio M, Satoh H, Katayama J, Takanashi S, Hashimoto K et al Discovery of the alphα7 nicotinic acetylcholine receptor agonists. (R)-30-(5-chlorothio-phen-2-yl)spiro-1-azabicyclo[2.2.2]octane-3,50-[10,30]ox azolidin-20-one as a novel, potent, selective, and orally bioavailable ligand. J Med Chem. 2005; 48 (7) 2678-86
  • 198 Taylor D. Pharmacokinetic interactions involving cloza-pine. Br J Psychiatry. 1997; 171: 109-12
  • 199 Tizabi Y, Ovestreet DH, Rezvani AH, Louis VA, Clark E, Janowsky DS et al Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology. 1999; 142: 193-9
  • 200 Tizabi Y, Rezvani AH, Russell LT, Tyler KY, Overstreet DH. Depressive characteristics of FSL rats: involvement of central nicotinic receptors. Pharmacol Biochem Behav. 2000; 66 (1) 73-7
  • 201 Tollefson GD. Cognitive function in schizophrenic pa tients. J Clin Psychiatry. 1996; 57 (11) 31-9
  • 202 Tregellas JR, Tanabe JL, Martin LF, Freedman R. FMRI of response to nicotine during a smooth pursuit eye movement task in schizophrenia. Am J Psychiatry. 2005; 162 (2) 391-3
  • 203 Vazquez-Palacios G, Bonilla-Jaime H, Velazquez-Moctezuma J. Antiepresant-like effects of the acute and chronic administration of nicotine in the rat forces swimming test and its interaction with fluoxetine. Pharmacol Biochem Behav. 2004; 78: 165-9
  • 204 Vazquez-Palacios G, Bonilla-Jaime H, Velazquez-Moctezuma J. Antiepresant effects of nicotine and fluoxetine in an animal model of depression induced by neonatal treat ment with clomipramine. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29 (1) 39-46
  • 205 Vogel GW, Hartley P, Neill D, Hagler M. A new animal model of endogenous depression: a summary of present finding. Neurosci Biobehav Rev. 1990; 14: 85-91
  • 206 Weinberger DR, Gallhofer B. Cognitive function in schizophrenia. Int Clin Psychopharmacol. 1997; 12 (04) 29-36
  • 207 Weiser M, Reichenberg A, Grotto I, Yasvitzky R, Rabinowitz J, Lubin G et al Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a his torical-prospective cohort study. Am J Psychiatr. 2004; 161 (7) 1219-23
  • 208 Westerink B. Can antipsychotic drugs be classified by their effects on a paricular group of dopamine neuron in the brain?. Eur J Pharmacol. 2002; 455: 1-18
  • 209 Wonnacott S, Irons J, Rapier C, Thorne B, Lunt GG. Pre-synaptic modulation of transmitter release by nicotinic receptors. In: Nordberg A, Fuxe K, Holmstedt B, Sundwall A. editors. Progress in brain research. vol. 79. Elsevier Science Publishers B. V.; 1989. p. 157-163
  • 210 Wonnacott S, Kaiser S, Mogg A, Soliakov L, Jones IW. Pre-synaptic nicotinic receptors modulating dopamine release in the rat striatum. Eur J Pharmacol. 2000; 393 (1–3) 51-8 [special issue].
  • 211 Woodruff-Pak DS, Green JT, Coleman-Valencia C, Pak JT. A nicotinic cholinergic agonist (GTS-21) and eyeblink classical conditioning: acquisition, retention, and relearn-ing in older rabbits. Esp Aging Re. 2000; 26 (4) 323-36
  • 212 Young J, Finlayson K, Spratt C, Marston H, Crawford N, Kelly J et al Nicotine improves sustained attention in mice: evidence for involvement of the alpha7 nicotinic acetylocholine receptor. Neuropsychopharmacology. 2004; 29 (5) 891-900
  • 213 Zhang W, Bymaster FP. The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D1, D2, D3, 5HT2A and muscarinic receptors. Psychopharmacology. 1999; 141 (3) 267-78
  • 214 Zullino DF, Delessert D, Eap CB, Presing M, Bauman P. Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine. Int Clin Psycho pharmacol. 2002; 17: 141-3