Skip to main content
SpringerLink
Log in

The role of 5-HT1a and 5-HT2a receptors in attention and motor control: a mechanistic study in healthy volunteers

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

Abstract

Rationale

Various studies have demonstrated a modulating role for serotonin in attention. Selective serotonin inhibitors have repeatedly been shown to impair performance in sustained attention tasks.

Objectives

To assess the contribution of serotonin reuptake inhibition and specific blockade of the pre-synaptic 5-HT1a receptor and the 5-HT2a receptor to deficits in attention.

Materials and methods

The study was conducted according to a randomized, double-blind, placebo controlled, four-way crossover design including 16 healthy volunteers. Treatments consisted of oral administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram 20 mg + placebo; escitalopram 20 mg + ketanserin (5-HT2a antagonist), 50 mg; escitalopram 20 mg + pindolol (5-HT1a antagonist) 10 mg; and placebo + placebo on four separate days. A range of performance tasks were conducted to assess the subjects’ attention and motor functions.

Results

Escitalopram administered alone impaired tracking performance in a divided attention task. The combination of escitalopram and pindolol and escitalopram and ketanserin impaired divided attention as compared to placebo. In addition, escitalopram and ketanserin impaired sustained attention. Divided attention impairment observed after combined treatments did not significantly differ from impairments after escitalopram alone. Sustained attention impairment observed after combined escitalopram and ketanserin significantly differed from escitalopram alone.

Conclusions

5HT1a blockade hardly affected SSRI effects on attention. Additional 5HT2a blockade, however, produced impairments of sustained attention and motor impulse control.

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

  • Aellig WH, Narjes HH, Nuesch E, Oertle RJ, Devos JE, Pacha W (1981) A pharmacodynamic and pharmacokinetic comparison of pindolol 20 mg retard and a conventional tablet. Eur J Clin Pharmacol 20:179–183

    Article  PubMed  CAS  Google Scholar 

  • Aronson S, Delgado P (2004) Escitalopram. Drugs Today (Bare) 40:121–131

  • Blokland A, Sik A, Lieben C (2005) Evaluation of DOI, 8-OH-DPAT, eticlopride and amphetamine on impulsive responding in a reaction time task in rats. Behav Pharmacol 16:93–100

    Article  PubMed  CAS  Google Scholar 

  • Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218

    Google Scholar 

  • Bortolozzi A, Diaz Mataix L, Scorza MC, Celada P, Artigas F (2005) The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity. J Neurochem 95:1597–1607

    Article  PubMed  CAS  Google Scholar 

  • Carli M, Samanin R (2000) The 5-HT(1A) receptor agonist 8-OH-DPAT reduces rats’ accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT(1A) receptors. Psychopharmacology 149:259–268

    Article  PubMed  CAS  Google Scholar 

  • Coull JT, Sahakian BJ, Middleton HC, Young AH, Park SB, McShane RH, Cowen PJ, Robbins TW (1995) Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion on focused attention and attentional search. Psychopharmacology 121:222–230

    Article  PubMed  CAS  Google Scholar 

  • de Wit H, Crean J, Richards JB (2000) Effects of d-amphetamine and ethanol on a measure of behavioral inhibition in humans. Behav Neurosci 114:830–837

    Article  PubMed  Google Scholar 

  • de Wit H, Enggasser JL, Richards JB (2002) Acute administration of d-amphetamine decreases impulsivity in healthy volunteers. Neuropsychopharmacology 27:813–825

    Article  PubMed  Google Scholar 

  • Di Matteo V, De Blasi A, Di Giulio C, Esposito E (2001) Role of 5-HT(2C) receptors in the control of central dopamine function. Trends Pharmacol Sci 22:229–232

    Article  PubMed  Google Scholar 

  • Esposito E (2006) Serotonin–dopamin interaction as a focus of novel antidepressant drugs. Current Drug Targets 7:177–185

    Article  PubMed  CAS  Google Scholar 

  • Harmer CJ, McTavish SFB, Clark L, Goodwin GM, Cowen PJ (2001) Tyrosine depletion attenuates dopamine function in healthy volunteers. Psychopharmacology 154:105–111

    Article  PubMed  CAS  Google Scholar 

  • Harrison AA, Everitt BJ, Robbins TW (1997) Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms. Psychopharmacology (Berl) 133:329–342

    Article  CAS  Google Scholar 

  • Harrison BJ, Olver JS, Norman TR, Burrows GD, Wesnes KA, Nathan PJ (2004) Selective effects of acute serotonin and catecholamine depletion on memory in healthy women. J Psychopharmacol 18:32–40

    Article  PubMed  CAS  Google Scholar 

  • Hedner T, Persson B, Berglund G (1983) Ketanserin, a novel 5-hydroxytryptamine antagonist: monotherapy in essential hypertension. Br J Clin Pharmacol 16:121–125

    PubMed  CAS  Google Scholar 

  • Jex HR, McDonnell, JD, Phatak AV (1966) A “critical” tracking task for man–machine research related to the operators effective delay time. Part I: theory and experiments with a first order divergent controlled element. NASA CR-616, NASA Contractor Report. NASA CR:100–105

  • Koelega HS (1993) Stimulant drugs and vigilance performance: a review. Psychopharmacology (Berl) 111:1–16

    Article  CAS  Google Scholar 

  • Liechti ME, Saur MR, Gamma A, Hell D, Vollenweider FX (2000) Psychological and physiological effects on MDMA ("Ecstasy") after pretreatment with the 5-HT(2) antagonist ketanserin in healthy humans. Neurophychopharmacology 23:396–404

    Google Scholar 

  • Logan GD (1994) On the ability to inhibit thought and action. In: Dagenbach D, Carr TH (eds) Inhibitory processes in attention, memory and language. Academic, San Diego

    Google Scholar 

  • Lucas G, Spampinato U (2000) Role of striatal serotonin2A and serotonin2C receptor subtypes in the control of in vivo dopamine outflow in the rat striatum. J Neurochem 74:693–701

    Article  PubMed  CAS  Google Scholar 

  • Mackworth NH (1950) Researches on the measurement of human performance. In: Sinaiko HW (ed) Selected papers on human factors in the design and use of control systems. Dover, New York, pp 174–331

    Google Scholar 

  • Matrenza C, Hughes JM, Kemp AH, Wesnes KA, Harrison BJ, Nathan PJ (2004) Simultaneous depletion of serotonin and catecholamines impairs sustained attention in healthy female subjects without affecting learning and memory. J Psychopharmacol (Oxf) 18:21–31

    Article  CAS  Google Scholar 

  • Moskowitz H (1973) Laboratory studies of the effects of alcohol on some variables related to driving. J Saf Res 5:185–192

    Google Scholar 

  • Mulder-Hajonides van der Meulen WREH (1981) Measurement of subjective sleep quality. Proceedings of the International European Sleep Congress. Elsevier, Amsterdam, The Netherlands

    Google Scholar 

  • Nicholson AN, Pascoe PA (1990) Dopaminergic transmission and the sleep–wakefulness continuum in man. Neuropharmacology 29:411–417

    Article  PubMed  CAS  Google Scholar 

  • O’Hanlon J, Robbe HWJ, Vermeeren A, VanLeeuwen C, Danjou PE (1998) Venlafaxine’s effects on healthy volunteers’ driving, psychomotor, and vigilance performance during 15-day fixed and incremental dosing regimens. J Clin Psychopharmacol 18:212–221

    Article  PubMed  CAS  Google Scholar 

  • Pribram KH, McGuinness D (1975) Arousal, activation, and effort in the control of attention. Psychol Rev 82:116–149

    Article  PubMed  CAS  Google Scholar 

  • Rabiner EA, Gunn RN, Wilkins MR, Sargent PA, Mocaer E, Sedman E, Cowen PJ, Grasby PM (2000) Drug action at the 5-HT(1A) receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-11C]WAY-100635. Nucl Med Biol 27:509–513

    Article  PubMed  CAS  Google Scholar 

  • Rabiner EA, Bhagwagar Z, Gunn RN, Sargent PA, Bench CJ, Cowen PJ, Grasby PM (2001) Pindolol augmentation of selective serotonin reuptake inhibitors: PET evidence that the dose used in clinical trials is too low. Am J Psychiatry 158:2080–2082

    Article  PubMed  CAS  Google Scholar 

  • Rabiner EA, Bhagwagar Z, Gunn RN, Cowen PJ, Grasby PM (2004) Preferential 5-HT1A autoreceptor occupancy by pindolol is attenuated in depressed patients: effect of treatment or an endophenotype of depression? Neuropsychopharmacology 29:1688–1698

    Article  PubMed  CAS  Google Scholar 

  • Ramaekers JG, Kuypers KPC (2006) Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on behavioral measures of impulsivity: alone and in combination with alcohol. Neuropsychopharmacology 31:1048–1055

    Article  PubMed  CAS  Google Scholar 

  • Ramaekers JG, Muntjewerff ND, O’Hanlon JF (1995) A comparative study of acute and subchronic effects of dothiepin, fluoxetine and placebo on psychomotor and actual driving performance. Br J Pharmacol 39:397–404

    CAS  Google Scholar 

  • Rasmussen K, McCreary AC, Shanks EA (2004) Attenuation of the effects of fluoxetine on serotonergic neuronal activity by pindolol in rats. Neurosci Lett 355:1–4

    Article  PubMed  CAS  Google Scholar 

  • Riedel WJ, Eikmans K, Heldens A, Schmitt JA (2005) Specific serotonergic reuptake inhibition impairs vigilance performance acutely and after subchronic treatment. J Psychopharmacol (Oxf) 19:12–20

    Article  CAS  Google Scholar 

  • Robbins TW (1997) Arousal systems and attentional processes. Biol Psychol 45:57–71

    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 

  • Schmitt JA, Jorissen BL, Sobczak S, van Boxtel MP, Hogervorst E, Deutz NE, Riedel WJ (2000) Tryptophan depletion impairs memory consolidation but improves focussed attention in healthy young volunteers. J Psychopharmacol (Oxf) 14:21–29

    CAS  Google Scholar 

  • Schmitt JA, Ramaekers JG, Kruizinga MJ, van Boxtel MP, Vuurman EF, Riedel WJ (2002) Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man. J Psychopharmacol (Oxf) 16:207–214

    Article  CAS  Google Scholar 

  • Soubrie P (1986) Reconciling the role of central serotonin neurons in human and animal behavior. Behav Brain Sci 9:319–364

    Google Scholar 

  • Spoont MR (1992) Modulatory role of serotonin in neural information processing: implications for human psychopathology. Psychol Bull 112:330–350

    Article  PubMed  CAS  Google Scholar 

  • Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18:643–662

    Article  Google Scholar 

  • Wingen M, Bothmer J, Langer S, Ramaekers JG (2005) Actual driving performance and psychomotor function in healthy subjects after acute and subchronic treatment with escitalopram, mirtazapine, and placebo: a crossover trial. J Clin Psychiatry 66:436–443

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful to Silke Conen and medical doctor C. J. van Leeuwen for their assistance in the data collection.

Author information

Authors and Affiliations

  1. Faculty of Psychology, Department of Neurocognition (Experimental Psychopharmacology Unit), Brain and Behaviour Institute, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands

    Marleen Wingen, Kim P. C. Kuypers & Johannes G. Ramaekers

Authors
  1. Marleen Wingen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kim P. C. Kuypers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Johannes G. Ramaekers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marleen Wingen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wingen, M., Kuypers, K.P.C. & Ramaekers, J.G. The role of 5-HT1a and 5-HT2a receptors in attention and motor control: a mechanistic study in healthy volunteers. Psychopharmacology 190, 391–400 (2007). https://doi.org/10.1007/s00213-006-0614-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0614-x

Keywords

Search

Navigation