SpringerLink
Log in

The serotonergic system in motor and non-motor manifestations of Parkinson’s disease

  • Review
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

The understanding of Parkinson’s disease (PD) classically revolves around dopamine depletion within the striatum. However, PD is a multi-systemic disease in which extra-dopaminergic systems are affected. The serotonergic (5-HT) system is one of these and has been extensively studied in PD. Although the 5-HT system uses one transporter (SERT) and 14 receptor sub-types, most of the studies in PD have focussed on SERT and serotonergic type 1A and 2A receptors (5-HT1A and 5-HT2A). Post-mortem autoradiographic binding studies and in vivo imaging studies have suggested an involvement of the 5-HT system in PD-related anxiety, depression, psychosis and L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. Pre-clinical and clinical pharmacological studies have shown that SERT blockade might effectively alleviate depression and dyskinesia and, more recently, might exert disease-modifying effects. Enhancing the physiological activity of 5-HT1A receptors with 5-HT1A agonists might alleviate anxiety, dyskinesia and tremor, although a deleterious effect on the anti-parkinsonian efficacy of L-DOPA may ultimately limit the use of this class of compounds. Enhanced 5-HT2A-mediated neurotransmission has been associated with depression, dyskinesia, psychosis and tremor. The current article critically reviews studies assessing the SERT, as well as 5-HT1A and 5-HT2A receptors in idiopathic PD and animal models of PD, and discusses unmet challenges to effectively treat manifestations of PD using SERT antagonists, 5-HT1A agonists and 5-HT2A antagonists.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • ACADIA (2013) ACADIA Pharmaceuticals announces expedited path to NDA filing for pimavanserin following meeting with FDA. http://phx.corporate-ir.net/phoenix.zhtml?c=125180&p=irol-newsArticle&ID=1805706 Accessed 14th April 2013

  • Albin RL, Koeppe RA, Bohnen NI, Wernette K, Kilbourn MA, Frey KA (2008) Spared caudal brainstem SERT binding in early Parkinson’s disease. J Cereb Blood Flow Metab 28:441–444

    PubMed  CAS  Google Scholar 

  • Antonini A, Tesei S, Zecchinelli A et al (2006) Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson’s disease and depression: effect on quality of life. Mov Disord 21:1119–1122

    PubMed  Google Scholar 

  • Arai R, Karasawa N, Geffard M, Nagatsu T, Nagatsu I (1994) Immunohistochemical evidence that central serotonin neurons produce dopamine from exogenous L-DOPA in the rat, with reference to the involvement of aromatic L-amino acid decarboxylase. Brain Res 667:295–299

    PubMed  CAS  Google Scholar 

  • Arai R, Karasawa N, Geffard M, Nagatsu I (1995) L-DOPA is converted to dopamine in serotonergic fibers of the striatum of the rat: a double-labeling immunofluorescence study. Neurosci Lett 195:195–198

    PubMed  CAS  Google Scholar 

  • Arai R, Karasawa N, Nagatsu I (1996) Aromatic L-amino acid decarboxylase is present in serotonergic fibers of the striatum of the rat. A double-labeling immunofluorescence study. Brain Res 706:177–179

    PubMed  CAS  Google Scholar 

  • Auff E, Birkmayer W, Brucke T et al (1987) Ritanserin in the treatment of tremor-dominant Parkinson’s disease: a preliminary study. New Trends Clin Neuropharmacol 1:149–158

    Google Scholar 

  • Ballanger B, Strafella AP, van Eimeren T, Zurowski M, Rusjan PM, Houle S, Fox SH (2010) Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol 67:416–421

    PubMed  Google Scholar 

  • Ballanger B, Klinger H, Eche J et al (2012) Role of serotonergic 1A receptor dysfunction in depression associated with Parkinson’s disease. Mov Disord 27:84–89

    PubMed  CAS  Google Scholar 

  • Bara-Jimenez W, Bibbiani F, Morris MJ, Dimitrova T, Sherzai A, Mouradian MM, Chase TN (2005) Effects of serotonin 5-HT1A agonist in advanced Parkinson’s disease. Mov Disord 20:932–936

    PubMed  Google Scholar 

  • Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083–1152

    PubMed  CAS  Google Scholar 

  • Baron MS, Dalton WB (2003) Quetiapine as treatment for dopaminergic-induced dyskinesias in Parkinson’s disease. Mov Disord 18:1208–1209

    PubMed  Google Scholar 

  • Bartoszyk GD, Van den Buuse M, Gerlach M, Riederer P (2006) Mechanism of the antidyskinetic efficacy of sarizotan in hemiparkinsonian rats [Abstract]. Mov Disord 21(Suppl 15):S495

    Google Scholar 

  • Bennett JP Jr, Landow ER, Schuh LA (1993) Suppression of dyskinesias in advanced Parkinson’s disease. II. Increasing daily clozapine doses suppress dyskinesias and improve parkinsonism symptoms. Neurology 43:1551–1555

    PubMed  Google Scholar 

  • Bennett JP Jr, Landow ER, Dietrich S, Schuh LA (1994) Suppression of dyskinesias in advanced Parkinson’s disease: moderate daily clozapine doses provide long-term dyskinesia reduction. Mov Disord 9:409–414

    PubMed  Google Scholar 

  • Berding G, Brucke T, Odin P et al (2003) [[123I]beta-CIT SPECT imaging of dopamine and serotonin transporters in Parkinson’s disease and multiple system atrophy. Nuklearmedizin 42:31–38

    PubMed  CAS  Google Scholar 

  • Berger B (1978) In vitro uptake of dopamine in serotoninergic nerve terminals: a fluorescence histochemical study on vibratome sections of the rat cerebral cortex. Adv Biochem Psychopharmacol 19:405–408

    PubMed  CAS  Google Scholar 

  • Berger B, Glowinski J (1978) Dopamine uptake in serotoninergic terminals in vitro: a valuable tool for the histochemical differentiation of catecholaminergic and serotoninergic terminals in rat cerebral structures. Brain Res 147:29–45

    PubMed  CAS  Google Scholar 

  • Bibbiani F, Oh JD, Chase TN (2001) Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology 57:1829–1834

    PubMed  CAS  Google Scholar 

  • Bishop C, Taylor JL, Kuhn DM, Eskow KL, Park JY, Walker PD (2006) MDMA and fenfluramine reduce L-DOPA-induced dyskinesia via indirect 5-HT1A receptor stimulation. Eur J Neurosci 23:2669–2676

    PubMed  Google Scholar 

  • Bishop C, Krolewski DM, Eskow KL, Barnum CJ, Dupre KB, Deak T, Walker PD (2009) Contribution of the striatum to the effects of 5-HT1A receptor stimulation in L-DOPA-treated hemiparkinsonian rats. J Neurosci Res 87:1645–1658

    PubMed  CAS  Google Scholar 

  • Bishop C, George JA, Buchta W et al (2012) Serotonin transporter inhibition attenuates l-DOPA-induced dyskinesia without compromising l-DOPA efficacy in hemi-parkinsonian rats. Eur J Neurosci 36:2839–2848

    PubMed  Google Scholar 

  • Boileau I, Warsh JJ, Guttman M et al (2008) Elevated serotonin transporter binding in depressed patients with Parkinson’s disease: a preliminary PET study with [11C]DASB. Mov Disord 23:1776–1780

    PubMed  Google Scholar 

  • Bonhaus D, MacFarland K, Willims H, Mills R (2009) Pimavanserin: a selective 5-HT2A inverse agonist has antipsychotic like activity in animal models of Parkinson’s disease (PD) and reduces psychotic symptoms in PD patients [Abstract]. Soc Neurosci

  • Bonifati V, Fabrizio E, Cipriani R, Vanacore N, Meco G (1994) Buspirone in levodopa-induced dyskinesias. Clin Neuropharmacol 17:73–82

    PubMed  CAS  Google Scholar 

  • Boyer EW, Shannon M (2005) The serotonin syndrome. N Engl J Med 352:1112–1120

    PubMed  CAS  Google Scholar 

  • Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211

    PubMed  Google Scholar 

  • Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134

    PubMed  Google Scholar 

  • Brandstadter D, Oertel WH (2002) Treatment of drug-induced psychosis with quetiapine and clozapine in Parkinson’s disease. Neurology 58:160–161

    PubMed  Google Scholar 

  • Brucke T, Kornhuber J, Angelberger P, Asenbaum S, Frassine H, Podreka I (1993) SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT. Binding kinetics in the human brain. J Neural Transm Gen Sect 94:137–146

    PubMed  CAS  Google Scholar 

  • Burstein ES, Ma J, Wong S et al (2005) Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther 315:1278–1287

    PubMed  CAS  Google Scholar 

  • Bymaster FP, Calligaro DO, Falcone JF et al (1996) Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 14:87–96

    PubMed  CAS  Google Scholar 

  • Caley CF, Friedman JH (1992) Does fluoxetine exacerbate Parkinson’s disease? J Clin Psychiatry 53:278–282

    PubMed  CAS  Google Scholar 

  • Caretti V, Stoffers D, Winogrodzka A et al (2008) Loss of thalamic serotonin transporters in early drug-naive Parkinson’s disease patients is associated with tremor: an [(123)I]beta-CIT SPECT study. J Neural Transm 115:721–729

    PubMed  CAS  Google Scholar 

  • Carlsson T, Carta M, Winkler C, Bjorklund A, Kirik D (2007) Serotonin neuron transplants exacerbate L-DOPA-induced dyskinesias in a rat model of Parkinson’s disease. J Neurosci 27:8011–8022

    PubMed  CAS  Google Scholar 

  • Carlsson T, Carta M, Munoz A, Mattsson B, Winkler C, Kirik D, Bjorklund A (2009) Impact of grafted serotonin and dopamine neurons on development of L-DOPA-induced dyskinesias in parkinsonian rats is determined by the extent of dopamine neuron degeneration. Brain 132:319–335

    PubMed  Google Scholar 

  • Carta M, Carlsson T, Kirik D, Bjorklund A (2007) Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain 130:1819–1833

    PubMed  Google Scholar 

  • Carta M, Carlsson T, Munoz A, Kirik D, Bjorklund A (2008) Serotonin-dopamine interaction in the induction and maintenance of L-DOPA-induced dyskinesias. Prog Brain Res 172:465–478

    PubMed  CAS  Google Scholar 

  • Ceravolo R, Nuti A, Piccinni A et al (2000) Paroxetine in Parkinson’s disease: effects on motor and depressive symptoms. Neurology 55:1216–1218

    PubMed  CAS  Google Scholar 

  • Chen CP, Alder JT, Bray L, Kingsbury AE, Francis PT, Foster OJ (1998) Post-synaptic 5-HT1A and 5-HT2A receptors are increased in Parkinson’s disease neocortex. Ann N Y Acad Sci 861:288–289

    PubMed  CAS  Google Scholar 

  • Chen P, Kales HC, Weintraub D, Blow FC, Jiang L, Mellow AM (2007) Antidepressant treatment of veterans with Parkinson’s disease and depression: analysis of a national sample. J Geriatr Psychiatry Neurol 20:161–165

    PubMed  Google Scholar 

  • Cheng AV, Ferrier IN, Morris CM et al (1991) Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer’s and Parkinson’s diseases. J Neurol Sci 106:50–55

    PubMed  CAS  Google Scholar 

  • Chinaglia G, Landwehrmeyer B, Probst A, Palacios JM (1993) Serotoninergic terminal transporters are differentially affected in Parkinson’s disease and progressive supranuclear palsy: an autoradiographic study with [3H]citalopram. Neuroscience 54:691–699

    PubMed  CAS  Google Scholar 

  • Chung YC, Kim SR, Park JY et al (2011) Fluoxetine prevents MPTP-induced loss of dopaminergic neurons by inhibiting microglial activation. Neuropharmacology 60:963–974

    PubMed  CAS  Google Scholar 

  • Connemann BJ, Schonfeldt-Lecuona C (2004) Ziprasidone in Parkinson’s disease psychosis. Can J Psychiatry 49:73

    PubMed  Google Scholar 

  • Dahlstroem A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand 232(Suppl):231–255

    Google Scholar 

  • D’Amato RJ, Zweig RM, Whitehouse PJ et al (1987) Aminergic systems in Alzheimer’s disease and Parkinson’s disease. Ann Neurol 22:229–236

    PubMed  Google Scholar 

  • Dekundy A, Lundblad M, Danysz W, Cenci MA (2007) Modulation of L-DOPA-induced abnormal involuntary movements by clinically tested compounds: further validation of the rat dyskinesia model. Behav Brain Res 179:76–89

    PubMed  CAS  Google Scholar 

  • Descarries L, Riad M (2012) Effects of the antidepressant fluoxetine on the subcellular localization of 5-HT1A receptors and SERT. Philos Trans R Soc Lond B Biol Sci 367:2416–2425

    PubMed  CAS  Google Scholar 

  • Dewey RB Jr, O’Suilleabhain PE (2000) Treatment of drug-induced psychosis with quetiapine and clozapine in Parkinson’s disease. Neurology 55:1753–1754

    PubMed  Google Scholar 

  • Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ (2003) Tremor in Parkinson’s disease and serotonergic dysfunction: an 11C-WAY 100635 PET study. Neurology 60:601–605

    PubMed  CAS  Google Scholar 

  • Dupre KB, Eskow KL, Negron G, Bishop C (2007) The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat. Brain Res 1158:135–143

    PubMed  CAS  Google Scholar 

  • Dupre KB, Eskow KL, Barnum CJ, Bishop C (2008) Striatal 5-HT1A receptor stimulation reduces D1 receptor-induced dyskinesia and improves movement in the hemiparkinsonian rat. Neuropharmacology 55:1321–1328

    PubMed  CAS  Google Scholar 

  • Dupre KB, Ostock CY, Eskow Jaunarajs KL, Button T, Savage LM, Wolf W, Bishop C (2011) Local modulation of striatal glutamate efflux by serotonin 1A receptor stimulation in dyskinetic, hemiparkinsonian rats. Exp Neurol 229:288–299

    PubMed  CAS  Google Scholar 

  • Durif F, Vidailhet M, Bonnet AM, Blin J, Agid Y (1995) Levodopa-induced dyskinesias are improved by fluoxetine. Neurology 45:1855–1858

    PubMed  CAS  Google Scholar 

  • Eskow KL, Gupta V, Alam S, Park JY, Bishop C (2007) The partial 5-HT(1A) agonist buspirone reduces the expression and development of l-DOPA-induced dyskinesia in rats and improves l-DOPA efficacy. Pharmacol Biochem Behav 87:306–314

    PubMed  CAS  Google Scholar 

  • Eskow KL, Dupre KB, Barnum CJ, Dickinson SO, Park JY, Bishop C (2009) The role of the dorsal raphe nucleus in the development, expression, and treatment of L-DOPA-induced dyskinesia in hemiparkinsonian rats. Synapse 63:610–620

    PubMed  CAS  Google Scholar 

  • Factor SA, Brown D (1992) Clozapine prevents recurrence of psychosis in Parkinson’s disease. Mov Disord 7:125–131

    PubMed  CAS  Google Scholar 

  • Factor SA, Friedman JH (1997) The emerging role of clozapine in the treatment of movement disorders. Mov Disord 12:483–496

    PubMed  CAS  Google Scholar 

  • Fahn S (2008) The history of dopamine and levodopa in the treatment of Parkinson’s disease. Mov Disord 23(Suppl 3):S497–S508

    PubMed  Google Scholar 

  • Fahn S, Libsch LR, Cutler RW (1971) Monoamines in the human neostriatum: topographic distribution in normals and in Parkinson’s disease and their role in akinesia, rigidity, chorea, and tremor. J Neurol Sci 14:427–455

    PubMed  CAS  Google Scholar 

  • Fahn S, Elton RL, Members of the UPDRS Development Committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease. Macmillan Healthcare Information, Florham Park, pp 153–163

    Google Scholar 

  • Fernandez HH, Trieschmann ME, Burke MA, Jacques C, Friedman JH (2003) Long-term outcome of quetiapine use for psychosis among Parkinsonian patients. Mov Disord 18:510–514

    PubMed  Google Scholar 

  • Fernandez HH, Trieschmann ME, Friedman JH (2004) Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Clin Neuropharmacol 27:4–5

    PubMed  CAS  Google Scholar 

  • Fox SH, Visanji N, Reyes G, Huot P, Gomez-Ramirez J, Johnston T, Brotchie JM (2010) Neuropsychiatric behaviors in the MPTP marmoset model of Parkinson’s disease. Can J Neurol Sci 37:86–95

    PubMed  Google Scholar 

  • Fregni F, Santos CM, Myczkowski ML et al (2004) Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:1171–1174

    PubMed  CAS  Google Scholar 

  • French Clozapine Parkinson Study Group (1999) Clozapine in drug-induced psychosis in Parkinson’s disease. The French Clozapine Parkinson Study Group. Lancet 353:2041–2042

    Google Scholar 

  • Friedman JH (1992) Fluoxetine in Parkinson’s disease [Abstract]. Mov Disord 7(Suppl 1):102

    Google Scholar 

  • Friedman JH, Factor SA (2000) Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson’s disease. Mov Disord 15:201–211

    PubMed  CAS  Google Scholar 

  • Friedman JH, Lannon MC (1989) Clozapine in the treatment of psychosis in Parkinson’s disease. Neurology 39:1219–1221

    PubMed  CAS  Google Scholar 

  • Friedman JH, Berman RM, Goetz CG et al (2006) Open-label flexible-dose pilot study to evaluate the safety and tolerability of aripiprazole in patients with psychosis associated with Parkinson’s disease. Mov Disord 21:2078–2081

    PubMed  Google Scholar 

  • Frisina PG, Haroutunian V, Libow LS (2009) The neuropathological basis for depression in Parkinson’s disease. Parkinsonism Relat Disord 15:144–148

    PubMed  Google Scholar 

  • Gatto EM, Fernandez Pardal M, Micheli F (1994) Exacerbation of parkinsonism caused by fluoxetine. Medicina (B Aires) 54:182

    CAS  Google Scholar 

  • Gerard C, Martres MP, Lefevre K et al (1997) Immuno-localization of serotonin 5-HT6 receptor-like material in the rat central nervous system. Brain Res 746:207–219

    PubMed  CAS  Google Scholar 

  • Gil S, Park C, Lee J, Koh H (2010) The roles of striatal serotonin and L: -amino-acid decarboxylase on L: -DOPA-induced Dyskinesia in a Hemiparkinsonian rat model. Cell Mol Neurobiol 30:817–825

    PubMed  CAS  Google Scholar 

  • Gil SJ, Park CH, Lee JE, Minn YK, Koh HC (2011) Positive association between striatal serotonin level and abnormal involuntary movements in chronic L-DOPA-treated hemiparkinsonian rats. Brain Res Bull 84:151–156

    PubMed  CAS  Google Scholar 

  • Gimenez-Roldan S, Navarro E, Mateo D (2003) Effects of quetiapine at low doses on psychosis motor disability and stress of the caregiver in patients with Parkinson’s disease. Rev Neurol 36:401–404

    PubMed  CAS  Google Scholar 

  • Goetz CG, Damier P, Hicking C et al (2007) Sarizotan as a treatment for dyskinesias in Parkinson’s disease: a double-blind placebo-controlled trial. Mov Disord 22:179–186

    PubMed  Google Scholar 

  • Gomez-Mancilla B, Bedard PJ (1993) Effect of nondopaminergic drugs on L-DOPA-induced dyskinesias in MPTP-treated monkeys. Clin Neuropharmacol 16:418–427

    PubMed  CAS  Google Scholar 

  • Gordon PH, Pullman SL, Louis ED, Frucht SJ, Fahn S (2002) Mirtazapine in Parkinsonian tremor. Parkinsonism Relat Disord 9:125–126

    PubMed  CAS  Google Scholar 

  • Gregoire L, Samadi P, Graham J, Bedard PJ, Bartoszyk GD, Di Paolo T (2009) Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-DOPA in parkinsonian monkeys. Parkinsonism Relat Disord 15:445–452

    PubMed  Google Scholar 

  • Guttman M, Boileau I, Warsh J et al (2007) Brain serotonin transporter binding in non-depressed patients with Parkinson’s disease. Eur J Neurol 14:523–528

    PubMed  CAS  Google Scholar 

  • Haapaniemi TH, Ahonen A, Torniainen P, Sotaniemi KA, Myllyla VV (2001) [123I]beta-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients. Mov Disord 16:124–130

    PubMed  CAS  Google Scholar 

  • Halliday GM, Blumbergs PC, Cotton RG, Blessing WW, Geffen LB (1990a) Loss of brainstem serotonin- and substance P-containing neurons in Parkinson’s disease. Brain Res 510:104–107

    PubMed  CAS  Google Scholar 

  • Halliday GM, Li YW, Blumbergs PC et al (1990b) Neuropathology of immunohistochemically identified brainstem neurons in Parkinson’s disease. Ann Neurol 27:373–385

    PubMed  CAS  Google Scholar 

  • Hammerstad JP, Carter J, Nutt JG, Casten GC, Shrotriya RC, Alms DR, Temple D (1986) Buspirone in Parkinson’s disease. Clin Neuropharmacol 9:556–560

    PubMed  CAS  Google Scholar 

  • Hauser RA, Zesiewicz TA (1997) Sertraline for the treatment of depression in Parkinson’s disease. Mov Disord 12:756–759

    PubMed  CAS  Google Scholar 

  • Hely MA, Morris JG, Reid WG, Trafficante R (2005) Sydney Multicenter Study of Parkinson’s disease: non-L-DOPA-responsive problems dominate at 15 years. Mov Disord 20:190–199

    PubMed  Google Scholar 

  • Henderson J, Yiannikas C, Graham JS (1992) Effect of ritanserin, a highly selective 5-HT2 receptor antagonist, on Parkinson’s disease. Clin Exp Neurol 29:277–282

    PubMed  CAS  Google Scholar 

  • Hildebrand J, Delecluse F (1987) Effect of ritanserin, a selective serotonin-S2 antagonist, on parkinsonian rest tremor. Curr Ther Res 41:298–300

    Google Scholar 

  • Hoglinger GU, Rizk P, Muriel MP, Duyckaerts C, Oertel WH, Caille I, Hirsch EC (2004) Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 7:726–735

    PubMed  Google Scholar 

  • Hornykiewicz O (2002) L-DOPA: from a biologically inactive amino acid to a successful therapeutic agent. Amino Acids 23:65–70

    PubMed  CAS  Google Scholar 

  • Hornykiewicz O, Kish SJ (1987) Biochemical pathophysiology of Parkinson’s disease. Adv Neurol 45:19–34

    PubMed  CAS  Google Scholar 

  • http://www.clinicaltrials.gov/ (NCT01174004) A study of the safety and efficacy of pimavanserin in patients with Parkinson’s disease psychosis. Accessed 14th April 2013

  • Huot P, Johnston TH, Darr T et al (2010a) Increased 5-HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations. Mov Disord 25:1399–1408

    PubMed  Google Scholar 

  • Huot P, Johnston TH, Koprich JB, Winkelmolen L, Fox SH, Brotchie JM (2010b) Regulation of cortical and striatal 5-HT(1A) receptors in the MPTP-lesioned macaque. Neurobiol Aging 1:491–512. doi:10.1016/j.neurobiolaging.2010.1009.1011

    Google Scholar 

  • Huot P, Fox SH, Brotchie JM (2011a) The serotonergic system in Parkinson’s disease. Prog Neurobiol 95:163–212

    PubMed  CAS  Google Scholar 

  • Huot P, Fox SH, Newman-Tancredi A, Brotchie JM (2011b) Anatomically-selective 5-HT1A and 5-HT2A therapies for Parkinson’s disease—an approach to reducing dyskinesia without exacerbating parkinsonism? J Pharmacol Exp Ther 339:1–7

    Google Scholar 

  • Huot P, Johnston TH, Lewis KD et al (2011c) Characterization of 3,4-methylenedioxymethamphetamine (mdma) enantiomers in vitro and in the mptp-lesioned primate: R-MDMA reduces severity of dyskinesia, whereas S-MDMA extends duration of on-time. J Neurosci 31:7190–7198

    PubMed  CAS  Google Scholar 

  • Huot P, Johnston TH, Visanji NP et al (2012a) Increased levels of 5-HT1A receptor binding in ventral visual pathways in Parkinson’s disease. Mov Disord 27:735–742

    PubMed  CAS  Google Scholar 

  • Huot P, Johnston TH, Winkelmolen L, Fox SH, Brotchie JM (2012b) 5-HT(2A) receptor levels increase in MPTP-lesioned macaques treated chronically with L-DOPA. Neurobiol Aging 33:194.e195-115

  • Iravani MM, Jackson MJ, Kuoppamaki M, Smith LA, Jenner P (2003) 3,4-methylenedioxymethamphetamine (ecstasy) inhibits dyskinesia expression and normalizes motor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates. J Neurosci 23:9107–9115

    PubMed  CAS  Google Scholar 

  • Iravani MM, Tayarani-Binazir K, Chu WB, Jackson MJ, Jenner P (2006) In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with increased motor disability. J Pharmacol Exp Ther 319:1225–1234

    PubMed  CAS  Google Scholar 

  • Jakeman LB, To ZP, Eglen RM, Wong EH, Bonhaus DW (1994) Quantitative autoradiography of 5-HT4 receptors in brains of three species using two structurally distinct radioligands, [3H]GR113808 and [3H]BIMU-1. Neuropharmacology 33:1027–1038

    PubMed  CAS  Google Scholar 

  • Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA (2002) The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol 441:137–140

    PubMed  CAS  Google Scholar 

  • Juncos JL, Arvanitis L, Sweitzer D, Yeung P, Jewart RD (1999) Quetiapine improves psychotic symptoms associated with Parkinson’s disease. Neurology 52(Suppl 2):A262

    Google Scholar 

  • Kannari K, Kurahashi K, Tomiyama M et al (2002) Tandospirone citrate, a selective 5-HT1A agonist, alleviates L-DOPA-induced dyskinesia in patients with Parkinson’s disease. No To Shinkei 54:133–137

    PubMed  Google Scholar 

  • Katzenschlager R, Manson AJ, Evans A, Watt H, Lees AJ (2004) Low dose quetiapine for drug induced dyskinesias in Parkinson’s disease: a double blind cross over study. J Neurol Neurosurg Psychiatry 75:295–297

    PubMed  CAS  Google Scholar 

  • Kim SE, Choi JY, Choe YS, Choi Y, Lee WY (2003) Serotonin transporters in the midbrain of Parkinson’s disease patients: a study with 123I-beta-CIT SPECT. J Nucl Med 44:870–876

    PubMed  CAS  Google Scholar 

  • Kish SJ, Tong J, Hornykiewicz O, Rajput A, Chang LJ, Guttman M, Furukawa Y (2008) Preferential loss of serotonin markers in caudate versus putamen in Parkinson’s disease. Brain 131:120–131

    PubMed  Google Scholar 

  • Klawans HL, Ringel SP (1973) A clinical study of methysergide in Parkinsonism: evidence against a serotonergic mechanism. J Neurol Sci 19:399–405

    PubMed  CAS  Google Scholar 

  • Kleedorfer B, Lees AJ, Stern GM (1991) Buspirone in the treatment of levodopa induced dyskinesias. J Neurol Neurosurg Psychiatry 54:376–377

    PubMed  CAS  Google Scholar 

  • Kohl Z, Winner B, Ubhi K et al (2012) Fluoxetine rescues impaired hippocampal neurogenesis in a transgenic A53T synuclein mouse model. Eur J Neurosci 35:10–19

    PubMed  Google Scholar 

  • Kuan WL, Zhao JW, Barker RA (2008) The role of anxiety in the development of levodopa-induced dyskinesias in an animal model of Parkinson’s disease, and the effect of chronic treatment with the selective serotonin reuptake inhibitor citalopram. Psychopharmacology 197:279–293

    PubMed  CAS  Google Scholar 

  • Kuno A, Ogawa T, Ikeguchi K, Fujimoto K, Nakano I (2001) Deterioration of parkinsonian symptoms and psychosis after fluvoxamine medication. Neurol Med 54:157–160

    Google Scholar 

  • Lavoie B, Parent A (1990) Immunohistochemical study of the serotoninergic innervation of the basal ganglia in the squirrel monkey. J Comp Neurol 299:1–16

    PubMed  CAS  Google Scholar 

  • Leentjens AF, Vreeling FW, Luijckx GJ, Verhey FR (2003) SSRIs in the treatment of depression in Parkinson’s disease. Int J Geriatr Psychiatry 18:552–554

    PubMed  CAS  Google Scholar 

  • Leo RJ (1996) Movement disorders associated with the serotonin selective reuptake inhibitors. J Clin Psychiatry 57:449–454

    PubMed  CAS  Google Scholar 

  • Linazasoro G (2000) Worsening of Parkinson’s disease by citalopram. Parkinsonism Relat Disord 6:111–113

    PubMed  Google Scholar 

  • Lindgren HS, Andersson DR, Lagerkvist S, Nissbrandt H, Cenci MA (2010) L-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson’s disease: temporal and quantitative relationship to the expression of dyskinesia. J Neurochem 112:1465–1476

    PubMed  CAS  Google Scholar 

  • Lopez-Meza E, Ruiz-Chow A, Ramirez-Bermudez J (2005) Aripiprazole in psychosis associated with Parkinson’s disease. J Neuropsychiatry Clin Neurosci 17:421–422

    PubMed  CAS  Google Scholar 

  • Ludwig CL, Weinberger DR, Bruno G, Gillespie M, Bakker K, LeWitt PA, Chase TN (1986) Buspirone, Parkinson’s disease, and the locus ceruleus. Clin Neuropharmacol 9:373–378

    PubMed  CAS  Google Scholar 

  • Lundblad M, Andersson M, Winkler C, Kirik D, Wierup N, Cenci MA (2002) Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson’s disease. Eur J Neurosci 15:120–132

    PubMed  CAS  Google Scholar 

  • Lundblad M, Usiello A, Carta M, Hakansson K, Fisone G, Cenci MA (2005) Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia. Exp Neurol 194:66–75

    PubMed  CAS  Google Scholar 

  • Maeda T, Yoshida J, Kudo K, Nagata K (2009) Systemic L-DOPA deplete the striatal serotonin release in rats with nigro-striatal dopaminergic denervation [Abstract]. Mov Disord 24(Suppl 1):S355–S356

    Google Scholar 

  • Maeda T, Yoshida J, Kudo K, Nagata K, Yamamoto M (2010) Systemic L-DOPA deplete the striatal serotonin release in rats with nigro-striatal dopaminergic denervation [Abstract]. Mov Disord 25(Suppl 2):S416

    Google Scholar 

  • Maertens de Noordhout A, Delwaide PJ (1986) Open pilot trial of ritanserin in parkinsonism. Clin Neuropharmacol 9:480–484

    PubMed  CAS  Google Scholar 

  • Maloteaux JM, Luabeya MK, Laterre EC, Javoy-Agid F, Agid Y, Laduron PM (1985) S2-serotonin receptors in frontal cortex of parkinsonian patients [Abstract]. J Neurol 32(Suppl):108

    Google Scholar 

  • Maloteaux JM, Laterre EC, Laduron PM, Javoy-Agid F, Agid Y (1988) Decrease of serotonin-S2 receptors in temporal cortex of patients with Parkinson’s disease and progressive supranuclear palsy. Mov Disord 3:255–262

    PubMed  CAS  Google Scholar 

  • Mann DM, Yates PO (1983) Pathological basis for neurotransmitter changes in Parkinson’s disease. Neuropathol Appl Neurobiol 9:3–19

    PubMed  CAS  Google Scholar 

  • Marin C, Aguilar E, Rodriguez-Oroz MC, Bartoszyk GD, Obeso JA (2009) Local administration of sarizotan into the subthalamic nucleus attenuates levodopa-induced dyskinesias in 6-OHDA-lesioned rats. Psychopharmacology 204:241–250

    PubMed  CAS  Google Scholar 

  • Marsden CD (1982) The mysterious motor function of the basal ganglia: the Robert Wartenberg Lecture. Neurology 32:514–539

    PubMed  CAS  Google Scholar 

  • McCance-Katz EF, Marek KL, Price LH (1992) Serotonergic dysfunction in depression associated with Parkinson’s disease. Neurology 42:1813–1814

    PubMed  CAS  Google Scholar 

  • Meco G, Marini S, Linfante I, Modarelli F, Agnoli A (1988) Controlled single-blind crossover study of ritanserin and placebo in L-DOPA-induced dyskinesias in Parkinson’s disease. Curr Ther Res 43:262–270

    Google Scholar 

  • Meco G, Bonifati V, Fabrizio E, Vanacore N (1994) Worsening of parkinsonism with fluvoxamine - two cases. Hum Psychopharmacol 9:439–441

    Google Scholar 

  • Meco G, Fabrizio E, Di Rezze S, Alessandri A, Pratesi L (2003) Mirtazapine in L-DOPA-induced dyskinesias. Clin Neuropharmacol 26:179–181

    PubMed  CAS  Google Scholar 

  • Meco G, Stirpe P, Edito F, Purcaro C, Valente M, Bernardi S, Vanacore N (2009) Aripiprazole in L-DOPA-induced dyskinesias: a one-year open-label pilot study. J Neural Transm 116:881–884

    PubMed  CAS  Google Scholar 

  • Meltzer HY, Kennedy J, Dai J, Parsa M, Riley D (1995) Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson’s disease. A high potency effect of clozapine. Neuropsychopharmacology 12:39–45

    PubMed  CAS  Google Scholar 

  • Menza MM, Palermo B, Mark M (1999) Quetiapine as an alternative to clozapine in the treatment of dopamimetic psychosis in patients with Parkinson’s disease. Ann Clin Psychiatry 11:141–144

    PubMed  CAS  Google Scholar 

  • Menza M, Marin H, Kaufman K, Mark M, Lauritano M (2004) Citalopram treatment of depression in Parkinson’s disease: the impact on anxiety, disability, and cognition. J Neuropsychiatry Clin Neurosci 16:315–319

    PubMed  CAS  Google Scholar 

  • Merims D, Balas M, Peretz C, Shabtai H, Giladi N (2006) Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson’s disease psychosis. Clin Neuropharmacol 29:331–337

    PubMed  CAS  Google Scholar 

  • Mills R, Revell S, Bahr D, Williams H, Johnson A, Friedman JH (2008) A double-blind, placebo-controlled, dose-escalation trial of pimavanserin in Parkinson’s disease and psychosis [Abstract]. Mov Disord 23(Suppl 1):S221–S222

    Google Scholar 

  • Montastruc JL, Fabre N, Blin O, Senard JM, Rascol O, Rascol A (1995) Does fluoxetine aggravate Parkinson’s disease? A pilot prospective study. Mov Disord 10:355–357

    PubMed  CAS  Google Scholar 

  • Morgante L, Epifanio A, Spina E et al (2002) Quetiapine versus clozapine: a preliminary report of comparative effects on dopaminergic psychosis in patients with Parkinson’s disease. Neurol Sci 23(Suppl 2):S89–S90

    PubMed  Google Scholar 

  • Muller T, Olanow CW, Nutt J, Hicking C, Laska E, Russ H (2006) The PADDY-2 study: the evaluation of sarizotan for treatment-associated dyskinesia in Parkinson’s disease patients. Mov Disord 21(Suppl. 15):S591

    Google Scholar 

  • Munoz A, Li Q, Gardoni F et al (2008) Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia. Brain 131:3380–3394

    PubMed  Google Scholar 

  • Murai T, Muller U, Werheid K et al (2001) In vivo evidence for differential association of striatal dopamine and midbrain serotonin systems with neuropsychiatric symptoms in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 13:222–228

    PubMed  CAS  Google Scholar 

  • Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA (1994) Effect of the R(−) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors. Neurosci Lett 177:111–115

    PubMed  CAS  Google Scholar 

  • Navailles S, Bioulac B, Gross C, De Deurwaerdere P (2010) Chronic L-DOPA therapy alters central serotonergic function and L-DOPA-induced dopamine release in a region-dependent manner in a rat model of Parkinson’s disease. Neurobiol Dis 41(2):585–590

    PubMed  Google Scholar 

  • Nevalainen N, Af Bjerken S, Lundblad M, Gerhardt GA, Stromberg I (2011) Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia. J Neurochem 118(1):12–23

    PubMed  CAS  Google Scholar 

  • Nichols DE, Nichols CD (2008) Serotonin receptors. Chem Rev 108:1614–1641

    PubMed  CAS  Google Scholar 

  • Nordstrom AL, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G (1995) D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry 152:1444–1449

    PubMed  CAS  Google Scholar 

  • Oh JD, Bibbiani F, Chase TN (2002) Quetiapine attenuates levodopa-induced motor complications in rodent and primate parkinsonian models. Exp Neurol 177:557–564

    PubMed  CAS  Google Scholar 

  • Ohama E, Ikuta F (1976) Parkinson’s disease: distribution of Lewy bodies and monoamine neuron system. Acta Neuropathol 34:311–319

    PubMed  CAS  Google Scholar 

  • Olanow CW, Damier P, Goetz CG et al (2004) Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). Clin Neuropharmacol 27:58–62

    PubMed  CAS  Google Scholar 

  • Ostock CY, Dupre KB, Eskow Jaunarajs KL et al (2011) Role of the primary motor cortex in l-DOPA-induced dyskinesia and its modulation by 5-HT1A receptor stimulation. Neuropharmacology 61:753–760

    PubMed  CAS  Google Scholar 

  • Pact V, Giduz T (1999) Mirtazapine treats resting tremor, essential tremor, and levodopa-induced dyskinesias. Neurology 53:1154

    PubMed  CAS  Google Scholar 

  • Palhagen SE, Carlsson M, Curman E, Walinder J, Granerus AK (2008) Depressive illness in Parkinson’s disease–indication of a more advanced and widespread neurodegenerative process? Acta Neurol Scand 117:295–304

    PubMed  CAS  Google Scholar 

  • Papavasilliou PS, Cotzias GC, McDowell FH, Rosal VL, Sheehan PJ (1978) Cyproheptadine in levodopa-induced dyskinesia in parkinsonism. Clin Pharmacol Ther 23:195–198

    PubMed  CAS  Google Scholar 

  • Paquette MA, Lewis JR, Meshul CK, Johnson SW, Berger SP (2009) Effects of 5-HT1A agonism and NDMA antagonism on L-DOPA-induced dyskinesia and sensorimotor behavior in the 6-OHDA rat [Abstract]. Soc Neurosci

  • Paquette MA, Martinez AA, Macheda T, Giuffrida A (2010) NMDA antagonism versus 5-HT1A agonism: suppressing L-DOPA-induced dyskinesia without exacerbating parkinsonism in the 6-OHDA rat [Abstract]. Soc Neurosci

  • Parent A, Descarries L, Beaudet A (1981) Organization of ascending serotonin systems in the adult rat brain. A radioautographic study after intraventricular administration of [3H]5-hydroxytryptamine. Neuroscience 6:115–138

    PubMed  CAS  Google Scholar 

  • Parkinson Study Group (1999) Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. The Parkinson Study Group. N Engl J Med 340:757–763

    Google Scholar 

  • Paulus W, Jellinger K (1991) The neuropathologic basis of different clinical subgroups of Parkinson’s disease. J Neuropathol Exp Neurol 50:743–755

    PubMed  CAS  Google Scholar 

  • Paumier KL, Siderowf AD, Auinger P et al (2012) Tricyclic antidepressants delay the need for dopaminergic therapy in early Parkinson’s disease. Mov Disord 27:880–887

    PubMed  CAS  Google Scholar 

  • Pavese N, Metta V, Bose SK, Chaudhuri KR, Brooks DJ (2010) Fatigue in Parkinson’s disease is linked to striatal and limbic serotonergic dysfunction. Brain 133:3434–3443

    Google Scholar 

  • Politis M, Wu K, Loane C, Kiferle L, Molloy S, Brooks DJ, Piccini P (2010a) Staging of serotonergic dysfunction in Parkinson’s disease: an in vivo 11C-DASB PET study. Neurobiol Dis 40:216–221

    PubMed  CAS  Google Scholar 

  • Politis M, Wu K, Loane C, Turkheimer FE, Molloy S, Brooks DJ, Piccini P (2010b) Depressive symptoms in PD correlate with higher 5-HTT binding in raphe and limbic structures. Neurology 75:1920–1927

    PubMed  CAS  Google Scholar 

  • Pollak P, Tison F, Rascol O et al (2004) Clozapine in drug induced psychosis in Parkinson’s disease: a randomised, placebo controlled study with open follow up. J Neurol Neurosurg Psychiatry 75:689–695

    PubMed  CAS  Google Scholar 

  • Prueter C, Habermeyer B, Norra C, Kosinski CM (2003) Akathisia as a side effect of antipsychotic treatment with quetiapine in a patient with Parkinson’s disease. Mov Disord 18:712–713

    PubMed  Google Scholar 

  • Raisman R, Cash R, Agid Y (1986) Parkinson’s disease: decreased density of 3H-imipramine and 3H-paroxetine binding sites in putamen. Neurology 36:556–560

    PubMed  CAS  Google Scholar 

  • Rampello L, Chiechio S, Raffaele R, Vecchio I, Nicoletti F (2002) The SSRI, citalopram, improves bradykinesia in patients with Parkinson’s disease treated with L-DOPA. Clin Neuropharmacol 25:21–24

    PubMed  CAS  Google Scholar 

  • Rascol O, Damier P, Goetz CG et al (2006) A large phase III study to evaluate the safety and efficacy of sarizotan in the treatment of L-DOPA-induced dyskinesia associated with Parkinson’s disease: the Paddy-1 study. Mov Disord 21(Suppl. 15):S492–S493

    Google Scholar 

  • Reddy S, Factor SA, Molho ES, Feustel PJ (2002) The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia. Mov Disord 17:676–681

    PubMed  Google Scholar 

  • Remy P, Doder M, Lees A, Turjanski N, Brooks D (2005) Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128:1314–1322

    PubMed  Google Scholar 

  • Riahi G, Morissette M, Parent M, Di Paolo T (2011) Brain 5-HT(2A) receptors in MPTP monkeys and levodopa-induced dyskinesias. Eur J Neurosci 33(10):1823–1831

    PubMed  Google Scholar 

  • Rich SS, Friedman JH, Ott BR (1995) Risperidone versus clozapine in the treatment of psychosis in six patients with Parkinson’s disease and other akinetic-rigid syndromes. J Clin Psychiatry 56:556–559

    PubMed  CAS  Google Scholar 

  • Richard IH, Kurlan R (1997) A survey of antidepressant drug use in Parkinson’s disease. Parkinson Study Group. Neurology 49:1168–1170

    PubMed  CAS  Google Scholar 

  • Richard IH, Kurlan R, Tanner C, Factor S, Hubble J, Suchowersky O, Waters C (1997) Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson’s disease. Parkinson Study Group. Neurology 48:1070–1077

    PubMed  CAS  Google Scholar 

  • Richard IH, McDermott MP, Kurlan R et al (2012) A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology 78:1229–1236

    PubMed  CAS  Google Scholar 

  • Richelson E, Souder T (2000) Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci 68:29–39

    PubMed  CAS  Google Scholar 

  • Ritter JL, Alexander B (1997) Retrospective study of selegiline-antidepressant drug interactions and a review of the literature. Ann Clin Psychiatry 9:7–13

    PubMed  CAS  Google Scholar 

  • Roberts C (2006) ACP-103, a 5-HT2A receptor inverse agonist. Curr Opin Investig Drugs 7:653–660

    PubMed  CAS  Google Scholar 

  • Rylander D, Parent M, O’Sullivan SS et al (2010) Maladaptive plasticity of serotonin axon terminals in levodopa-induced dyskinesia. Ann Neurol 68:619–628

    PubMed  CAS  Google Scholar 

  • Scatton B, Javoy-Agid F, Rouquier L, Dubois B, Agid Y (1983) Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease. Brain Res 275:321–328

    PubMed  CAS  Google Scholar 

  • Schonfeldt-Lecuona C, Connemann BJ (2004) Aripiprazole and Parkinson’s disease psychosis. Am J Psychiatry 161:373–374

    PubMed  Google Scholar 

  • Seeman P, Tallerico T (1999) Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am J Psychiatry 156:876–884

    PubMed  CAS  Google Scholar 

  • Seppi K, Weintraub D, Coelho M et al (2011) The Movement Disorder Society Evidence-Based Medicine Review Update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord 26(Suppl 3):S42–S80

    PubMed  Google Scholar 

  • Sharp SI, Ballard CG, Ziabreva I et al (2008) Cortical serotonin 1A receptor levels are associated with depression in patients with dementia with Lewy bodies and Parkinson’s disease dementia. Dement Geriatr Cogn Disord 26:330–338

    PubMed  CAS  Google Scholar 

  • Strecker K, Wegner F, Hesse S et al (2011) Preserved serotonin transporter binding in de novo Parkinson’s disease: negative correlation with the dopamine transporter. J Neurol 258:19–26

    PubMed  CAS  Google Scholar 

  • Suzuki K, Okada K, Wakuda T et al (2010) Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferation in rats: reversal by fluoxetine. PLoS ONE 5:e9260

    PubMed  Google Scholar 

  • Tani Y, Ogata A, Koyama M, Inoue T (2010) Effects of piclozotan (SUN N4057), a partial serotonin 1A receptor agonist, on motor complications induced by repeated administration of levodopa in parkinsonian rats. Eur J Pharmacol 649:218–223

    PubMed  CAS  Google Scholar 

  • Tesei S, Antonini A, Canesi M, Zecchinelli A, Mariani CB, Pezzoli G (2000) Tolerability of paroxetine in Parkinson’s disease: a prospective study. Mov Disord 15:986–989

    PubMed  CAS  Google Scholar 

  • Thomas AA, Friedman JH (2010) Current use of clozapine in Parkinson disease and related disorders. Clin Neuropharmacol 33:14–16

    PubMed  CAS  Google Scholar 

  • Trappler B, Friedman S (1998) Treatment of depression in Parkinson’s disease in the very old. J Pharm Tech 14:110–115

    CAS  Google Scholar 

  • Trosch RM, Group CC (1996) Clozapine use in Parkinson’s disease [Abstract]. Neurology 46:A375–A376

    Google Scholar 

  • Trosch RM, Friedman JH, Lannon MC et al (1998) Clozapine use in Parkinson’s disease: a retrospective analysis of a large multicentered clinical experience. Mov Disord 13:377–382

    PubMed  CAS  Google Scholar 

  • Vanover KE, Weiner DM, Makhay M et al (2006) Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropylo xy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther 317:910–918

    PubMed  CAS  Google Scholar 

  • Vanover KE, Betz AJ, Weber SM et al (2008) A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model. Pharmacol Biochem Behav 90:540–544

    PubMed  CAS  Google Scholar 

  • Visanji NP, Gomez-Ramirez J, Johnston TH, Pires D, Voon V, Brotchie JM, Fox SH (2006) Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson’s disease. Mov Disord 21:1879–1891

    PubMed  Google Scholar 

  • Weiner WJ, Minagar A, Shulman LM (2000) Quetiapine for l-DOPA-induced psychosis in PD. Neurology 54:1538

    PubMed  CAS  Google Scholar 

  • Wermuth L, Sorensen PS, Timm S et al (1998) Depression in idiopathic Parkinson’s disease treated with citalopram—A placebo-controlled trial. Nord J Psychiatry 52:163–169

    Google Scholar 

  • Wickremaratchi M, Morris HR, Ali IM (2006) Aripiprazole associated with severe exacerbation of Parkinson’s disease. Mov Disord 21:1538–1539

    PubMed  Google Scholar 

  • Wilson JM, Levey AI, Rajput A et al (1996) Differential changes in neurochemical markers of striatal dopamine nerve terminals in idiopathic Parkinson’s disease. Neurology 47:718–726

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The present work was supported by The Cure Parkinson Trust and Krembil Neuroscience Fund.

Conflict of interest

There are no financial disclosures relevant to this review article and no conflict of interest. SHF has received consultancy fees from Merck, Merck Serono, Teva. PH has received consultancy fees from Atuka Inc.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, University of Montréal, Montreal, QC, Canada

    Philippe Huot

  2. Notre-Dame Hospital, Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada

    Philippe Huot

  3. Division of Neurology, Toronto Western Hospital, Movement Disorder Clinic McL 7-421, University of Toronto, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada

    Susan H. Fox

Authors
  1. Philippe Huot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan H. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susan H. Fox.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huot, P., Fox, S.H. The serotonergic system in motor and non-motor manifestations of Parkinson’s disease. Exp Brain Res 230, 463–476 (2013). https://doi.org/10.1007/s00221-013-3621-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-013-3621-2

Keywords

Search

Navigation