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Haloperidol 2 mg impairs inhibition but not visuospatial attention

Abstract

Rationale

The dopaminergic system has been implicated in visuospatial attention and inhibition, but the exact role has yet to be elucidated. Scarce literature suggests that attenuation of dopaminergic neurotransmission negatively affects attentional focusing and inhibition. To the best of our knowledge, this is the first study that evaluated the effect of dopaminergic antagonism on stopping performance.

Methods

Dopaminergic neurotransmission was attenuated in 28 healthy male participants by using 2 mg haloperidol. A repeated-measures placebo-controlled crossover design was implemented, and performance indices of attention and inhibition were assessed in the visual spatial cueing task (VSC) and stop signal task (SST). Additionally, the effect of haloperidol on motoric parameters was assessed. It was expected that haloperidol as contrasted to placebo would result in a reduction of the “validity effect,” the benefit of valid cueing as opposed to invalid cueing of a target in terms of reaction time. Furthermore, an increase in stop signal reaction time (SSRT) in the SST was expected.

Results and conclusion

Results partially confirmed the hypothesis. Haloperidol negatively affected inhibitory motor control in the SST as indexed by SSRT, but there were no indications that haloperidol affected bias or disengagement in the VSC task as indicated by a lack of an effect on RTs. Pertaining to secondary parameters, motor activity increased significantly under haloperidol. Haloperidol negatively affected reaction time variability and errors in both tasks, as well as omissions in the SST, indicating a decreased sustained attention, an increase in premature responses, and an increase in lapses of attention, respectively.

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References

  • Arnsten AFT (2004) Adrenergic targets for the treatment of cognitive deficits in schizophrenia. Psychopharmacology 174:25–31. doi:10.1007/s00213-003-1724-3

    CAS  Article  PubMed  Google Scholar 

  • Arnsten AF, Mathew R, Ubriani R et al (1999) Alpha-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function. Biol Psychiatry 45:26–31

    CAS  Article  PubMed  Google Scholar 

  • Aron AR, Fletcher PC, Bullmore ET et al (2003) Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nat Neurosci 6:115–116. doi:10.1038/nn1003

    CAS  Article  PubMed  Google Scholar 

  • Aron AR, Robbins TW, Poldrack RA (2014) Inhibition and the right inferior frontal cortex: one decade on. Trends Cogn Sci 18:177–185. doi:10.1016/j.tics.2013.12.003

    Article  PubMed  Google Scholar 

  • Bari A, Robbins TW (2013) Noradrenergic versus dopaminergic modulation of impulsivity, attention and monitoring behaviour in rats performing the stop-signal task: possible relevance to ADHD. Psychopharmacology 230:89–111. doi:10.1007/s00213-013-3141-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Bari A, Eagle DM, Mar AC et al (2009) Dissociable effects of noradrenaline, dopamine, and serotonin uptake blockade on stop task performance in rats. Psychopharmacology 205:273–283. doi:10.1007/s00213-009-1537-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Bekker EM, Overtoom CC, Kenemans JL et al (2005) Stopping and changing in adults with ADHD. Psychol Med 35:807–816

    CAS  Article  PubMed  Google Scholar 

  • Caligiuri MP, Lohr JB, Ruck RK (1998) Scaling of movement velocity: a measure of neuromotor retardation in individuals with psychopathology. Psychophysiology 35:431–437

    CAS  Article  PubMed  Google Scholar 

  • Castellanos FX, Tannock R (2002) Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 3:617–628. doi:10.1038/nrn896

    CAS  Article  PubMed  Google Scholar 

  • Clark CR, Geffen GM, Geffen LB (1989) Catecholamines and the covert orientation of attention in humans. Neuropsychologia 27:131–139

    CAS  Article  PubMed  Google Scholar 

  • Colzato LS, Jongkees BJ, Sellaro R et al (2014) Eating to stop: tyrosine supplementation enhances inhibitory control but not response execution. Neuropsychologia 62:398–402. doi:10.1016/j.neuropsychologia.2013.12.027

    Article  PubMed  Google Scholar 

  • Corbetta M, Shulman GL (2002) Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci 3:201–215. doi:10.1038/nrn755

    CAS  Article  PubMed  Google Scholar 

  • Corbetta M, Patel G, Shulman GL (2008) The reorienting system of the human brain: from environment to theory of mind. Neuron 58:306–324. doi:10.1016/j.neuron.2008.04.017

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Coull JT, Nobre AC, Frith CD (2001) The noradrenergic alpha2 agonist clonidine modulates behavioural and neuroanatomical correlates of human attentional orienting and alerting. Cereb Cortex N Y N 11:73–841991

    CAS  Article  Google Scholar 

  • de Jong R, Coles MG, Logan GD, Gratton G (1990) In search of the point of no return: the control of response processes. J Exp Psychol Hum Percept Perform 16:164–182. doi:10.1037/0096-1523.16.1.164

    Article  PubMed  Google Scholar 

  • De Jong R, Coles MG, Logan GD (1995) Strategies and mechanisms in nonselective and selective inhibitory motor control. J Exp Psychol Hum Percept Perform 21:498–511

    CAS  Article  PubMed  Google Scholar 

  • Eagle DM, Wong JCK, Allan ME et al (2011) Contrasting roles for dopamine D1 and D2 receptor subtypes in the dorsomedial striatum but not the nucleus accumbens core during behavioral inhibition in the stop-signal task in rats. J Neurosci 31:7349–7356. doi:10.1523/JNEUROSCI.6182-10.2011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Ghahremani DG, Lee B, Robertson CL et al (2012) Striatal dopamine D2/D3 receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans. J Neurosci 32:7316–7324. doi:10.1523/JNEUROSCI.4284-11.2012

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Gurvich CT, Rossell SL (2014) Genetic variations in dopamine and inhibitory control: lack of influence on action restraint. Behav Brain Res 267:12–16. doi:10.1016/j.bbr.2014.03.015

    CAS  Article  PubMed  Google Scholar 

  • Janno S, Holi MM, Tuisku K, Wahlbeck K (2008) Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns. BMC Neurol 8:10. doi:10.1186/1471-2377-8-10

    Article  PubMed  PubMed Central  Google Scholar 

  • Kapur S, Zipursky R, Jones C et al (2000) Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 157:514–520

    CAS  Article  PubMed  Google Scholar 

  • Kenemans JL (2015) Specific proactive and generic reactive inhibition. Neurosci Biobehav Rev 56:115–126. doi:10.1016/j.neubiorev.2015.06.011

    Article  PubMed  Google Scholar 

  • Kenemans JL, Kähkönen S (2011) How human electrophysiology informs psychopharmacology: from bottom-up driven processing to top-down control. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 36:26–51. doi:10.1038/npp.2010.157

    CAS  Article  Google Scholar 

  • Kenemans JL, Bekker EM, Lijffijt M et al (2005) Attention deficit and impulsivity: selecting, shifting, and stopping. Int J Psychophysiol 58:59–70. doi:10.1016/j.ijpsycho.2005.03.009

    CAS  Article  PubMed  Google Scholar 

  • Kroeze WK, Hufeisen SJ, Popadak BA et al (2003) H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 28:519–526. doi:10.1038/sj.npp.1300027

    CAS  Article  Google Scholar 

  • Kumari V, Corr PJ, Mulligan OF et al (1997) Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man. Psychopharmacology 129:271–276

    CAS  Article  PubMed  Google Scholar 

  • Kumari V, Cotter PA, Mulligan OF et al (1999) Effects of d-amphetamine and haloperidol on latent inhibition in healthy male volunteers. J Psychopharmacol Oxf Engl 13:398–405

    CAS  Article  Google Scholar 

  • Lansbergen MM, Böcker KBE, Bekker EM, Kenemans JL (2007) Neural correlates of stopping and self-reported impulsivity. Clin Neurophysiol Off J Int Fed Clin Neurophysiol 118:2089–2103. doi:10.1016/j.clinph.2007.06.011

    Article  Google Scholar 

  • Leysen JE, Janssen PM, Gommeren W et al (1992) In vitro and in vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone. Mol Pharmacol 41:494–508

    CAS  PubMed  Google Scholar 

  • Lijffijt M, Kenemans JL, ter Wal A et al (2006) Dose-related effect of methylphenidate on stopping and changing in children with attention-deficit/hyperactivity disorder. Eur Psychiatry J Assoc Eur Psychiatr 21:544–547. doi:10.1016/j.eurpsy.2005.04.003

    Article  Google Scholar 

  • Logan GD, Cowan WB, Davis KA (1984) On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform 10:276–291

    CAS  Article  PubMed  Google Scholar 

  • Logemann HNA, Böcker KBE, Deschamps PKH et al (2013) The effect of noradrenergic attenuation by clonidine on inhibition in the stop signal task. Pharmacol Biochem Behav 110:104–111. doi:10.1016/j.pbb.2013.06.007

    CAS  Article  PubMed  Google Scholar 

  • Logemann HNA, Böcker KBE, Deschamps PKH et al (2014) The effect of attenuating noradrenergic neurotransmission by clonidine on brain activity measures of visuospatial attention. Hum Psychopharmacol Clin Exp 29:46–54. doi:10.1002/hup.2367

    CAS  Article  Google Scholar 

  • Mangun GR, Hillyard SA (1991) Modulations of sensory-evoked brain potentials indicate changes in perceptual processing during visual-spatial priming. J Exp Psychol Hum Percept Perform 17:1057–1074. doi:10.1037/0096-1523.17.4.1057

    CAS  Article  PubMed  Google Scholar 

  • Meinke A, Thiel CM, Fink GR (2006) Effects of nicotine on visuo-spatial selective attention as indexed by event-related potentials. Neuroscience 141:201–212. doi:10.1016/j.neuroscience.2006.03.072

    CAS  Article  PubMed  Google Scholar 

  • Nandam LS, Hester R, Wagner J et al (2011) Methylphenidate but not atomoxetine or citalopram modulates inhibitory control and response time variability. Biol Psychiatry 69:902–904. doi:10.1016/j.biopsych.2010.11.014

    CAS  Article  PubMed  Google Scholar 

  • Nyberg S, Nordström AL, Halldin C, Farde L (1995) Positron emission tomography studies on D2 dopamine receptor occupancy and plasma antipsychotic drug levels in man. Int Clin Psychopharmacol 10(Suppl 3):81–85

    PubMed  Google Scholar 

  • Overtoom CCE, Bekker EM, van der Molen MW et al (2009) Methylphenidate restores link between stop-signal sensory impact and successful stopping in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 65:614–619. doi:10.1016/j.biopsych.2008.10.048

    CAS  Article  PubMed  Google Scholar 

  • Posner MI, Snyder CR, Davidson BJ (1980) Attention and the detection of signals. J Exp Psychol 109:160–174

    CAS  Article  PubMed  Google Scholar 

  • Potter AS, Bucci DJ, Newhouse PA (2012) Manipulation of nicotinic acetylcholine receptors differentially affects behavioral inhibition in human subjects with and without disordered baseline impulsivity. Psychopharmacology 220:331–340. doi:10.1007/s00213-011-2476-0

    CAS  Article  PubMed  Google Scholar 

  • Ramdani C, Carbonnell L, Vidal F, Béranger C, Dagher A, Hasbroucq T (2015) Dopamine precursors depletion impairs impulse control in healthy volunteers. Psychopharmacology 232(2):477–487

  • Richelson E, Nelson A (1984) Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol 103:197–204

    CAS  Article  PubMed  Google Scholar 

  • Saeedi H, Remington G, Christensen BK (2006) Impact of haloperidol, a dopamine D2 antagonist, on cognition and mood. Schizophr Res 85:222–231. doi:10.1016/j.schres.2006.03.033

    Article  PubMed  Google Scholar 

  • Schmajuk M, Liotti M, Busse L, Woldorff MG (2006) Electrophysiological activity underlying inhibitory control processes in normal adults. Neuropsychologia 44:384–395. doi:10.1016/j.neuropsychologia.2005.06.005

    Article  PubMed  Google Scholar 

  • Schotte A, Janssen PF, Gommeren W et al (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology 124:57–73

    CAS  Article  PubMed  Google Scholar 

  • Simon JR, Wolf JD (1963) Choice reaction time as a function of angular stimulus-response correspondence and age. Ergonomics 6(1):99–105

  • Tannock R, Schachar RJ, Carr RP, Chajczyk D, Logan GD (1989) Effects of methylphenidate on inhibitory control in hyperactive children. J Abnorm Child Psychol 17(5):473–491

  • Thiel CM, Fink GR (2008) Effects of the cholinergic agonist nicotine on reorienting of visual spatial attention and top-down attentional control. Neuroscience 152:381–390. doi:10.1016/j.neuroscience.2007.10.061

    CAS  Article  PubMed  Google Scholar 

  • Thiel CM, Zilles K, Fink GR (2005) Nicotine modulates reorienting of visuospatial attention and neural activity in human parietal cortex. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 30:810–820. doi:10.1038/sj.npp.1300633

    CAS  Google Scholar 

  • van der Lubbe RHJ, Neggers SFW, Verleger R, Kenemans JL (2006) Spatiotemporal overlap between brain activation related to saccade preparation and attentional orienting. Brain Res 1072:133–152. doi:10.1016/j.brainres.2005.11.087

    Article  PubMed  Google Scholar 

  • Verbruggen F, Chambers CD, Logan GD (2013) Fictitious inhibitory differences: how skewness and slowing distort the estimation of stopping latencies. Psychol Sci 24:352–362. doi:10.1177/0956797612457390

    Article  PubMed  PubMed Central  Google Scholar 

  • Volkow ND, Wang G-J, Kollins SH et al (2009) Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA 302:1084–1091. doi:10.1001/jama.2009.1308

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Vossel S, Thiel CM, Fink GR (2008) Behavioral and neural effects of nicotine on visuospatial attentional reorienting in non-smoking subjects. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 33:731–738. doi:10.1038/sj.npp.1301469

    CAS  Article  Google Scholar 

  • Wald, F.D.M. (1984) De verkorte POMS. Master’s thesis.

  • Wald FDM, Mellenbergh GJ (1990) Instrumenteel onderzoek. Ned Tijdschr Voor Psychol 45:86–90

    Google Scholar 

  • Witte EA, Davidson MC, Marrocco RT (1997) Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance. Psychopharmacology 132:324–334

    CAS  Article  PubMed  Google Scholar 

  • Zetterström T, Sharp T, Collin AK, Ungerstedt U (1988) In vivo measurement of extracellular dopamine and DOPAC in rat striatum after various dopamine-releasing drugs; implications for the origin of extracellular DOPAC. Eur J Pharmacol 148:327–334

    Article  PubMed  Google Scholar 

  • Zirnheld PJ, Carroll CA, Kieffaber PD et al (2004) Haloperidol impairs learning and error-related negativity in humans. J Cogn Neurosci 16:1098–1112. doi:10.1162/0898929041502779

    Article  PubMed  Google Scholar 

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Correspondence to H.N. Alexander Logemann.

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Logemann, H.A., Böcker, K.B., Deschamps, P.K. et al. Haloperidol 2 mg impairs inhibition but not visuospatial attention. Psychopharmacology 234, 235–244 (2017). https://doi.org/10.1007/s00213-016-4454-z

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  • DOI: https://doi.org/10.1007/s00213-016-4454-z

Keywords

  • Dopaminergic
  • Dopamine
  • Haloperidol
  • Inhibition
  • Attention
  • Motor activity