Skip to main content
SpringerLink
Log in

Sensorimotor effects of pergolide, a dopamine agonist, in healthy subjects: a lateralized readiness potential study

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Objective

The major purpose of the present study was to further elucidate dopaminergic modulation of sensorimotor processing in healthy human subjects.

Materials and Methods

To more specifically analyze dopaminergic effects on premotor and motor stages of sensorimotor processing, lateralized readiness potentials (LRPs) were obtained. In a randomized double-blind crossover design, either 0.075 mg of the D1/D2 dopamine (DA) agonist pergolide or placebo were administered to 12 healthy male volunteers ranging from 19 to 25 years in age. The subjects performed a two-choice visual reaction time task. In addition to behavioral measures, such as response speed and error rate, stimulus-locked LRP (S-LRP) and response-locked LRP (LRP-R) latencies were determined. To better dissociate potential central and peripheral motor effects, measures of response dynamics and response-locked electromyogram (EMG-R) recordings were also obtained.

Observations

Pergolide reliably enhanced speed of stimulus-related information processing as indicated by shorter S-LRP latencies while LRP-R latencies, reaction time, and indicators of response dynamics were not influenced by DA agonistic treatment. Furthermore, lower EMG-R amplitudes and an increased number of wrong-hand responses were observed under pergolide compared to placebo.

Conclusion

The results indicate that dopaminergic neurotransmission effectively modulates early perceptual and cognitive stages of information processing as suggested by neural network models of the functional role of prefrontal DA. The lack of an effect on aspects of motor processing may be due to a higher capacity of the nigrostriatal compared to the mesocortical DA system to compensate pharmacologically induced changes in dopaminergic activity.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Agid Y (1991) Parkinson’s disease: pathophysiology. Lancet 337:1321–1324

    Article  PubMed  CAS  Google Scholar 

  • Alexander G, DeLong M, Strick P (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381

    Article  PubMed  CAS  Google Scholar 

  • Anderson JR (1980) Cognitive psychology and its implications. Freeman, San Francisco

    Google Scholar 

  • Arnott WL, Chenery HJ, Murdoch,BE, Silburn PA (2001) Semantic priming in Parkinson’s disease: evidence for delayed spreading activation. J Clin Exp Neuropsychol 23:502–519

    PubMed  CAS  Google Scholar 

  • Barch DM (2004) Pharmacological manipulation of human working memory. Psychopharmacology 174:126–135

    Article  PubMed  CAS  Google Scholar 

  • Bloxham CA, Dick DJ, Moore M (1987) Reaction times and attention in Parkinson’s disease. J Neurol Neurosurg Psychiatry 50:1178–1783

    PubMed  CAS  Google Scholar 

  • Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS (1982) Domperidone. A review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the treatment of chronic dyspepsia and as an antiemetic. Drugs 24:360–400

    Article  PubMed  CAS  Google Scholar 

  • Boraud T, Bezard E, Bioulac B, Gross CE (2002) From single extracellular unit recording in experimental and human Parkinsonism to the development of a functional concept of the role played by the basal ganglia in motor control. Prog Neurobiol 66:265–283

    Article  PubMed  Google Scholar 

  • Brumaghim JT, Klorman R, Strauss J, Lewine JD, Goldstein MG (1987) Does methylphenidate affect information processing? Findings from two studies on performance and p3b latency. Psychophysiology 24:361–373

    Article  PubMed  CAS  Google Scholar 

  • Castner SA, Goldman-Rakic PS, Williams GV (2004) Animal models of working memory: insights for targeting cognitive dysfunction in schizophrenia. Psychopharmacology 174:111–125

    Article  PubMed  CAS  Google Scholar 

  • Coles MGH (1989) Modern mind-brain reading: psychophysiology, physiology, and cognition. Psychophysiology 26:251–269

    Article  PubMed  CAS  Google Scholar 

  • Cooper JA, Sagar HJ, Tidswell P, Jordan N (1994) Slowed central processing in simple and go/no-go reaction time tasks in Parkinson’s disease. Brain 117:517–529

    Article  PubMed  Google Scholar 

  • Costall B, Fortune DH, Naylor RJ (1979) Neuropharmacological studies on the neuroleptic potential of domperidone (R33812). J Pharm Pharmacol 31:344–347

    PubMed  CAS  Google Scholar 

  • Crofts HS, Dalley JW, Collins P, van Denderen JC, Everitt BJ, Robbins TW, Roberts AC (2001) Differential effects of 6-OHDA lesions of the frontal cortex and caudate nucleus on the ability to acquire an attentional set. Cereb Cortex 11:1015–1026

    Article  PubMed  CAS  Google Scholar 

  • Deco G, Rolls ET (2003) Attention and working memory: a dynamical model of neuronal activity in the prefrontal cortex. Eur J Neurosci 18:2374–2390

    Article  PubMed  Google Scholar 

  • Evarts EV, Teräväinen H, Calne DB (1981) Reaction time in Parkinson’s disease. Brain 104:167–186

    Article  PubMed  CAS  Google Scholar 

  • Fitzpatrick P, Klorman R, Brumaghim JT, Keefover RW (1988) Effects of methylphenidate on stimulus evaluation and response processes: evidence from performance and event-related potentials. Psychophysiology 25:292–304

    Article  PubMed  CAS  Google Scholar 

  • Frank MJ (2005) Dynamic dopamine modulation in the basal ganglia: a neurocomputational account of cognitive deficits in medicated and non-medicated Parkinsonism. J Cogn Neurosci 17:51–72

    Article  PubMed  Google Scholar 

  • Giray M, Ulrich R (1993) Motor coactivation revealed by response force in divided and focused attention. J Exp Psychol Hum Percept Perform 19:1278–1291

    Article  PubMed  CAS  Google Scholar 

  • Goldman-Rakic PS, Bergson C, Mrzljak L, Williams GV (1997) Dopamine receptors and cognitive functions. In: KA Neve, RL Neve (eds) The dopamine receptors. Humana, Totowa, NJ, pp 499–522

    Google Scholar 

  • Gratton G, Coles MHG, Sirevaag EJ, Eriksen CW, Donchin E (1988) Pre- and poststimulus activation of response channels: a psychophysiological analysis. J Exp Psychol Hum Percept Perform 14:331–344

    Article  PubMed  CAS  Google Scholar 

  • Grübel-MathylU (1986) Effects of neuroleptics on aspects relevant to driving fitness. In: JF O’Hanlon, LL de Gier (eds) Drugs and driving. Taylor and Francis, London, pp 241–247

    Google Scholar 

  • Harden DG, Grace AA (1995) Activation of dopamine cell firing by repeated l-dopa administration to dopamine-depleted rats: its potential role in mediating the therapeutic response to l-dopa treatment. J Neurosci 15:6157–6166

    PubMed  CAS  Google Scholar 

  • Heffner TG, Zigmond MJ, Stricker EM (1977) Effects of dopaminergic agonists and antagonists on feeding in intact and 6-hydroxydopamine-treated rats. J Pharmacol Exp Ther 14:380–399

    Google Scholar 

  • Heilman KM, Bowers D, Watson RT, Greer M (1976) Reaction times in Parkinson’s disease. Arch Neurol 33:139–140

    PubMed  CAS  Google Scholar 

  • Jahanshahi M, Brown RGB, Marsden CD (1992) Simple and choice reaction time and the use of partial information for motor preparation in Parkinson’s disease. Brain 115:539–564

    Article  PubMed  Google Scholar 

  • Jasper HH (1958) Report of the committee on methods of clinical examination in electroencephalography. Electroencephalogr Clin Neurophysiol 86:176–182

    Google Scholar 

  • Jenner P (1995) The rationale for the use of dopamine agonists in Parkinson’s disease. Neurology 45(Suppl 3):S86–S112

    Google Scholar 

  • Kahkonen S, Ahveninen J, Jaaskelainen IP, Kaakkola S, Näätänen R, Huttunen J, Pekkonen E (2001) Effects of haloperidol on selective attention: a combined whole-head MEG and high-resolution EEG study. Neuropsychopharmacology 25:498–504

    Article  PubMed  CAS  Google Scholar 

  • Kutas M, Donchin E (1980) Preparation to respond as manifested by movement-related brain potentials. Brain Res 202:95–115

    PubMed  CAS  Google Scholar 

  • Low KA, Miller J, Vierck E (2002) Response slowing in Parkinson’s disease. A psychophysiological analysis of premotor and motor processes. Brain 125:1980–1994

    Article  PubMed  Google Scholar 

  • Luthringer R, Rinaudo G, Toussaint M, Bailey P, Muller G, Muzet A Macher J (1999) Electroencephalographic characterization of brain dopaminergic stimulation by apomorphine in healthy volunteers. Neuropsychobiology 39:49–56

    Article  PubMed  CAS  Google Scholar 

  • Mandir AS, Vaughan C (2000) Pathophysiology of Parkinson’s disease. Int Rev Psychiatry 12:270–280

    Article  Google Scholar 

  • Markham A, Benfield P (1997) Pergolide. A review of its pharmacology and therapeutic use in Parkinson’s disease. CNS Drugs 7:328–340

    Article  CAS  Google Scholar 

  • Marsden CD (1992) Dopamine and basal ganglia disorders in humans. Semin Neurosci 4:109–118

    Article  Google Scholar 

  • Miller J (1988) Discrete and continuous models of human information processing: theoretical distinctions and empirical results. Acta Psychol 67:191–257

    Article  CAS  Google Scholar 

  • Miller J, Patterson T, Ulrich R (1998) Jackknife-based method for measuring LRP onset latency differences. Psychophysiology 35:99–115

    Article  PubMed  CAS  Google Scholar 

  • Mink JW (1996) The basal ganglia: focused selection and inhibition of competing motor programs. Prog Neurobiol 50:381–425

    Article  PubMed  CAS  Google Scholar 

  • Müller U, von Cramon Y, Pollmann S (1998) D1- versus D2-receptor modulation of visuospatial working memory in humans. J Neurosci 18:2720–2728

    PubMed  Google Scholar 

  • Mueller-Gethmann H, Rinkenauer G, Stahl J, Ulrich R (2000) Preparation of response force and movement direction: onset effects on the lateralized readiness potential. Psychophysiology 37:507–514

    Article  Google Scholar 

  • Näätänen R (1971) Non-aging fore-periods and simple reaction time. Acta Psychol 35:316–327

    Article  Google Scholar 

  • Naylor H, Halliday R, Callaway E (1985) The effect of methylphenidate on information processing. Psychopharmacology 86:90–95

    Article  PubMed  CAS  Google Scholar 

  • Niemi P, Näätänen R (1981) Foreperiod and simple reaction time. Psychol Bull 89:133–162

    Article  Google Scholar 

  • Oades RD (1985) The role of noradrenaline in turning and dopamine in switching between signals in the CNS. Neurosci Biobehav Rev 9:261–282

    Article  PubMed  CAS  Google Scholar 

  • Oertel WH, Quinn NP (1996) Parkinsonism. In: Brandt T, Caplan LR, Dichgans J, Diener HC, Kennard C (eds) Neurological disorders: course and treatment. Academic, San Diego, pp 715–772

    Google Scholar 

  • Olanow CW, Fahn S, Muenter M, Klawans H, Hurtig H, Stern M, Shoulson I, Kurlan R, Grimes JD, Jankovic J (1994) A multicenter double-blind placebo-controlled trial of pergolide as an adjunct to Sinemet in Parkinson’s disease. Mov Disord 9:40–47

    Article  PubMed  CAS  Google Scholar 

  • Osman A, Moore CM (1993) The locus of dual-task interference: psychological refractory effects on movement-related brain potentials. J Exp Psychol Hum Percept Perform 19:1–21

    Google Scholar 

  • Osman A, Moore CM, Ulrich R (1995) Bisecting RT with lateralized readiness potentials: precue effects after LRP onset. Acta Psychol 90:111–127

    Article  Google Scholar 

  • Osman A, Moore CM, Ulrich R (2003) Temporal organization of covert motor processes during response selection and preparation. Biol Psychol 64:47–75

    Article  PubMed  Google Scholar 

  • Piercey MF, Hoffmann WE, Smith MW, Hyslop DK (1996) Inhibition of dopamine neuron firing by pramipexole, a dopamine D3 receptor-preferring agonist: comparison to other dopamine receptor agonists. Eur J Pharmacol 312:35–44

    Article  PubMed  CAS  Google Scholar 

  • Picton TW, Lins OG, Scherg M (1995) The recording and analysis of event-related potentials. In: Boller F, Grafman J (eds) Handbook of neuropsychology, vol 10. Elsevier, Amsterdam, pp 3–73

    Google Scholar 

  • Rafal RD, Inhoff AW, Friedman JH, Bernstein E (1987) Programming and execution of sequential movements in Parkinson’s disease. J Neurol Neurosurg Psychiatry 50:1267–1273

    Article  PubMed  CAS  Google Scholar 

  • Rammsayer T (1989) Is there a common dopaminergic basis of time perception and reaction time? Neuropsychobiology 21:37–42

    Article  PubMed  CAS  Google Scholar 

  • Rammsayer T (1997) Are there dissociable roles of the mesostriatal and mesolimbocortical dopamine systems on temporal information processing in humans? Neuropsychobiology 35:36–45

    Article  PubMed  CAS  Google Scholar 

  • Rihet P, Possamaï C-A, Micallef-Roll J, Blin O, Hasbroucq T (2002) Dopamine and human information processing: a reaction-time analysis of the effect of levodopa in healthy subjects. Psychopharmacology 163:62–67

    Article  PubMed  CAS  Google Scholar 

  • Robbins TW (2000) Chemical neuromodulation of frontal-executive functions in humans and other animals. Exp Brain Res 133:130–138

    Article  PubMed  CAS  Google Scholar 

  • Saint-Cyr JA (2003) Frontal–striatal circuit functions: context, sequence, and consequence. J Int Neuropsychol Soc 9:103–128

    PubMed  Google Scholar 

  • Sanders AF (1977) Structural and functional aspects of the reaction process. In: Dornic S (ed) Attention and performance VI. Erlbaum, New York, pp 3–25

    Google Scholar 

  • Sanders AF (1983) Towards a model of stress and human performance. Acta Psychol 53:61–97

    Article  CAS  Google Scholar 

  • Schück S, Bentué-Ferrer D, Kleinermans D, Reymann J-M, Polard E, Gandon J-M, Allain H (2002) Psychomotor and cognitive effects of piribedil, a dopamine agonist, in young healthy volunteers. Fundam Clin Pharmacol 16:57–65

    Article  PubMed  Google Scholar 

  • Seamans JK, Yang CR (2003) The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog Neurobiol 74:1–57

    Article  CAS  Google Scholar 

  • Seiss E, Praamstra P (2004) The basal ganglia and inhibitory mechanisms in response selection: evidence from subliminal priming of motor responses in Parkinson’s disease. Brain 127:330–339

    Article  PubMed  Google Scholar 

  • Servan-Schreiber D, Prinz H, Cohen JD (1990) A network model of catecholamine effects: gain, signal-to-noise ratio, and behavior. Science 249:892–895

    Article  PubMed  CAS  Google Scholar 

  • Servan-Schreiber D, Carter CS, Bruno RM, Cohen JD (1998a) Dopamine and the mechanisms of cognition: Part I. A neural network model predicting dopamine effects on selective attention. Biol Psychiatry 43:713–722

    Article  PubMed  CAS  Google Scholar 

  • Servan-Schreiber D, Carter CS, Bruno RM, Cohen JD (1998b) Dopamine and the mechanisms of cognition: Part II. d-Amphetamine effects in human subjects performing a selective attention task. Biol Psychiatry 43:723–729

    Article  PubMed  CAS  Google Scholar 

  • Stahl J, Gibbons H (2004) The application of jackknife-based onset detection of lateralized readiness potential in correlative approaches. Psychophysiology 41:845–860

    Article  PubMed  Google Scholar 

  • Sternberg S (1969) The discovery of processing stages: extensions of Donder’s method. Acta Psychol 30:276–315

    Article  Google Scholar 

  • Sternberg S (2001) Separate modifiability of mental modules and the use of pure and composite measures to reveal them. Acta Psychol 106:147–246

    Article  CAS  Google Scholar 

  • Stricker EM, Zigmond MJ (1986) Brain monoamines, homeostasis, and adaptive behavior. In: American Physiological Society (ed) Handbook of physiology, section 1. The nervous system, vol IV. Intrinsic regulatory systems of the brain. American Physiological Society, Bethesda, Maryland, pp 677–700

    Google Scholar 

  • Ulrich R, Mattes S, Miller J (1999) Donder’s assumption of pure insertion: an evaluation on the basis of response dynamics. Acta Psychol 102:43–75

    Article  Google Scholar 

  • van der Molen MW, Bashore TR, Halliday R, Callaway E (1991) Chronopsychophysiology: mental chronometry augmented by psychophysiological time markers. In: Jennings JR, Coles MGH (eds) Handbook of cognitive psychophysiology: central and automatic nervous system approaches. Wiley, Chichester, pp 9–178

    Google Scholar 

  • Volkow ND, Gur RC, Wang G-J, Fowler JS, Moberg PJ, Ding Y-S, Hitzemann R, Smith G, Logan J (1998) Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatr 155:344–349

    PubMed  CAS  Google Scholar 

  • Wascher E, Verleger R, Vieregge P, Jaskowski P, Koch S, Kompf D (1997) Responses to cued signals in Parkinson’s disease: distinguishing between disorders of cognition and of activation. Brain 120:1355–1375

    Article  PubMed  Google Scholar 

  • Winterer G, Weinberger DR (2004) Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends Neurosci 27:683–690

    Article  PubMed  CAS  Google Scholar 

  • Zigmond MJ, Heffner TG, Stricker EM (1980) The effect of altered dopaminergic activity on food intake in the rat: evidence for an optimal level of dopaminergic activity for behavior. Prog Neuro-Psychopharmacol 4:351–362

    Article  CAS  Google Scholar 

Download references

Acknowledgement

This study was supported by the German–American Academic Council Foundation (Grant TransCoop-Program 2000).

Author information

Authors and Affiliations

  1. Georg-Elias-Müller-Institut für Psychologie, Universität Göttingen, Gosslerstr. 14, 37073, Göttingen, Germany

    Thomas Rammsayer & Jutta Stahl

Authors
  1. Thomas Rammsayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jutta Stahl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Rammsayer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rammsayer, T., Stahl, J. Sensorimotor effects of pergolide, a dopamine agonist, in healthy subjects: a lateralized readiness potential study. Psychopharmacology 187, 36–46 (2006). https://doi.org/10.1007/s00213-006-0400-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0400-9

Keywords

Search

Navigation