Nervenheilkunde 2017; 36(09): 695-701
DOI: 10.1055/s-0038-1627516
Universitätsklinikum Ulm
Schattauer GmbH

Pharmakologisches kognitives Neuroenhancement und Neurotransmittersysteme

Pharmacological cognitive neuroenhancement and neurotransmitter systems
H. Graf
1   Universitätsklinikum Ulm, Klinik für Psychiatrie und Psychotherapie III, Ulm
,
K. Malejko
1   Universitätsklinikum Ulm, Klinik für Psychiatrie und Psychotherapie III, Ulm
,
Z. Sosic-Vasic
1   Universitätsklinikum Ulm, Klinik für Psychiatrie und Psychotherapie III, Ulm
,
M. Gahr
1   Universitätsklinikum Ulm, Klinik für Psychiatrie und Psychotherapie III, Ulm
› Author Affiliations
Further Information

Publication History

eingegangen am: 02 July 2017

angenommen am: 13 July 2017

Publication Date:
20 January 2018 (online)

Zusammenfassung

Unter pharmakologischem kognitiven Neuroenhancement (PKN) versteht man die Einnahme von Substanzen von Gesunden zur kognitiven Leistungssteigerung, ohne dass damit eine präventive oder therapeutische Absicht verfolgt wird. Epidemiologische Daten zeigen für Deutschland eine steigende Prävalenz von PKN in den vergangenen Jahren und es werden unter den verschreibungspflichtigen Medikamenten vorwiegend Substanzen eingenommen, die das cholinerge, dopaminerge und noradrenerge System modulieren. Wir gehen in diesem Artikel neben den neuroanatomischen und neurofunktionellen Aspekten dieser drei Neurotransmittersysteme vorwiegend auf Befunde zur Wirksamkeit von Antidementiva, Methylphenidat und Modafinil bei Gesunden ein. Des Weiteren werden allgemeine Prinzipien des pharmakologischen kognitiven Neuroenhancements und medizinisch-ethische Aspekte aufgeführt und diskutiert.

Summary

Pharmacological cognitive neuroenhancement (PCN) refers to the intake of prescription drugs by healthy subjects to improve cognitive functions without any therapeutic or preventive intention, and recent epidemiological data suggest an increase in prevalence of PCN in German population. Particularly, prescription drug modulating the cholinergic, dopaminergic and noradrenergic system were used for PCN. Thus, here we focus on neuroanatomical and neurofunctional aspects of the respective neurotransmitter systems and provide evidence for the efficacy of antidementia, methylphenidate, and modafinil to improve cognitive functions in healthy subjects. Moreover, we introduce common principles of pharmacological cognitive neuroenhancement and point on several aspects of a still ongoing ethical debate.

 
  • Literatur

  • 1 Galert T, Bublitz C, Heuser I, Merkel R, Repantis D, Schöne-Seifert B, Talbot D. Das optimierte Gehirn. Gehirn & Geist 2009; 11: 1-12.
  • 2 Wilens TE, Adler LA, Adams J, Sgambati S, Rotrosen J, Sawtelle R, Utzinger L, Fusillo S. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008; 47: 21-31.
  • 3 Maher B. Poll results: look who’s doping. Nature 2008; 452: 674-675.
  • 4 Marschall J, Nolting HD, Hildebrandt S, Sydow H. Gesundheitsreport 2015. Analyse der Arbeitsunfähigkeitsdaten. Update: Doping am Arbeitsplatz. DAK Gesundheit. 2015
  • 5 Mesulam MM, Mufson EJ, Levey AI, Wainer BH. Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 1983; 214: 170-197.
  • 6 Sarter M, Parikh V. Choline transporters, cholinergic transmission and cognition. Nat Rev Neurosci 2005; 06: 48-56.
  • 7 Newman EL, Gupta K, Climer JR, Monaghan CK, Hasselmo ME. Cholinergic modulation of cognitive processing: insights drawn from computational models. Front Behav Neurosci 2012; 06: 1-19.
  • 8 Hasselmo ME. Neuromodulation: acetylcholine and memory consolidation. Trends Cognitive Sci 1999; 03: 351-359.
  • 9 Deutsch JA. The cholinergic synapse and the site of memory. Science 1971; 174: 788-794.
  • 10 Drachman DA. Memory and cognitive function in man: does the cholinergic system have a specific role?. Neurology 1977; 27: 783-790.
  • 11 Blokland A, Honig W, Raaijmakers WGM. Effects of intra-hippocampal scopolamine injections in a repeated spatial acquisition task in the rat. Psychopharmacology 1992; 109: 373-376.
  • 12 Rogers JL, Kesner RP. Cholinergic modulation of the hippocampus during encoding and retrieval. Neurobiol Learn Mem 2003; 80: 332-342.
  • 13 Bentley P, Driver J, Dolan RJ. Cholinergic modulation of cognition: insights from human pharmacological functional neuroimaging. Prog Neurobiol 2011; 94: 360-388.
  • 14 Yesavage JA, Mumenthaler MS, Taylor JL, Friedman L, O’Hara R, Sheikh J, Tinklenberg J, Whitehouse PJ. Donepezil and flight simulator performance: effects on retention of complex skills. Neurology 2002; 59: 123-125.
  • 15 Grön G, Kirstein M, Thielscher A, Riepe MW, Spitzer M. Cholinergic enhancement of episodic memory in healthy young adults. Psychopharmacology (Berl) 2005; 182: 170-179.
  • 16 Beglinger LJ, Tangphao-Daniels O, Kareken DA, Zhang L, Mohs R, Siemers ER. Neuropsychological test performance in healthy elderly volunteers before and after donepezil administration: a randomized, controlled study. J Clin Psychopharmacol 2005; 25: 159-165.
  • 17 Repantis D, Laisney O, Heuser I. Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res 2010; 61: 473-481.
  • 18 Stathis M, Scheffel U, Lever SZ, Boja JW, Carroll FI, Kuhar MJ. Rate of binding of various inhibitors at the dopamine transporter in vivo. Psychopharmacology (Berl) 1995; 119: 376-384.
  • 19 Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ. Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 2002; 06: 31-43.
  • 20 Wenthur CJ. Classics in Chemical Neuroscience: Methylphenidate. ACS Chem Neurosci 2016; 07: 1030-1040.
  • 21 Engert V, Pruessner JC. Dopaminergic and noradrenergic contributions to functionality in ADHD: the role of methylphenidate. Curr Neuropharmacol 2008; 06: 322-328.
  • 22 Arnsten AF. Catecholamine modulation of prefrontal cortical cognitive function. Trends Cogn Sci 1998; 02: 436-447.
  • 23 Hegarty SV, Sullivan AM, O’Keeffe GW. Midbrain dopaminergic neurons: a review of the molecular circuitry that regulates their development. Dev Biol 2013; 379: 123-138.
  • 24 Robbins TW, Arnsten AF. The neuropsychopharmacology of fronto-executivefunction: monoaminergic modulation. Annu Rev Neurosci 2009; 32: 267-287.
  • 25 Repantis D, Schlattmann P, Laisney O, Heuser I. Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacol Res 2010; 62: 187-206.
  • 26 Caviola L, Faber NS. Pills or Push-Ups? Effectiveness and Public Perception of Pharmacological and Non-Pharmacological Cognitive Enhancement. Front Psychol 2015; 06: 1-8.
  • 27 Ilieva IP, Hook CJ, Farah MJ. Prescription Stimulants’ Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Metaanalysis. J Cogn Neurosci 2015; 27: 1069-1089.
  • 28 Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin JF, Sahakian BJ, Robbins TW. Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology (Berl) 1999; 146: 482-491.
  • 29 Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, Hamilton C, Spencer RC. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry 2006; 60: 1111-1120.
  • 30 Berridge CW, Mitton E, Clark W, Roth RH. Engagement in a nonescape (displacement) behavior elicits a selective and lateralized suppression of frontal cortical dopaminergic utilization in stress. Synapse 1999; 32: 187-197.
  • 31 Arnsten AF. Catecholamine influences on dorsolateral prefrontal cortical networks. Biol Psychiatry 2011; 69: 89-99.
  • 32 Finke K, Dodds CM, Bublak P, Regenthal R, Baumann F, Manly T, Müller U. Effects of modafinil and methylphenidate on visual attention capacity: a TVA-based study. Psychopharmacology (Berl) 2010; 210: 317-329.
  • 33 Madras BK, Xie Z, Lin Z, Jassen A, Panas H, Lynch L, Johnson R, Livni E, Spencer TJ, Bonab AA, Miller GM, Fischman AJ. Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. J Pharmacol Exp Ther 2006; 319: 561-569.
  • 34 Minzenberg MJ, Carter CS. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsycho-pharmacology 2008; 33: 1477-1502.
  • 35 Qu WM, Huang ZL, Xu XH, Matsumoto N, Urade Y. Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. J Neurosci 2008; 28: 8462-8469.
  • 36 Berridge CW, Waterhouse BD. The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 2003; 42: 33-84.
  • 37 Aston-Jones G, Cohen JD. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 2005; 28: 403-450.
  • 38 Battleday RM, Brem AK. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. Eur Neuropsychopharmacol 2015; 25: 1865-1881.
  • 39 Minzenberg MJ, Watrous AJ, Yoon JH, Ursu S, Carter CS. Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI. Science 2008; 322: 1700-1702.
  • 40 Müller U, Steffenhagen N, Regenthal R, Bublak P. Effects of modafinil on working memory processes in humans. Psychopharmacology (Berl) 2004; 177: 161-169.
  • 41 Chamberlain SR, Hampshire A, Müller U, Rubia K, Del Campo N, Craig K, Regenthal R, Suckling J, Roiser JP, Grant JE, Bullmore ET, Robbins TW, Sahakian BJ. Atomoxetine modulates right inferior frontal activation during inhibitory control: a pharmacological functional magnetic resonance imaging study. Biol Psychiatry 2009; 65: 550-555.
  • 42 Graf H, Abler B, Freudenmann R, Beschoner P, Schaeffeler E, Spitzer M, Schwab M, Grön G. Neural correlates of error monitoring modulated by atomoxetine in healthy volunteers. Biol Psychiatry 2011; 69: 890-897.
  • 43 Farah MJ. Neuroethics: the practical and the philosophical. Trends Cogn Sci 2005; 09: 34-40.
  • 44 Knutson B, Wolkowitz OM, Cole SW, Chan T, Moore EA, Johnson RC, Terpstra J, Turner RA, Reus VI. Selective alteration of personality and social behavior by serotonergic intervention. Am J Psychiatry 1998; 155: 373-379.
  • 45 de Jongh R, Bolt I, Schermer M, Olivier B. Botox for the brain: enhancement of cognition, mood and pro-social behavior and blunting of unwanted memories. Neurosci Biobehav Rev 2008; 32: 760-776.
  • 46 Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM. Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry 2004; 161: 1256-1263.
  • 47 Wadsworth EJ, Moss SC, Simpson SA, Smith AP. SSRIs and cognitive performance in a working sample. Hum Psychopharmacol 2005; 20: 561-572.
  • 48 Schmitt JA, Kruizinga MJ, Riedel WJ. Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors. J Psychopharmacol 2001; 15: 173-179.
  • 49 Graf H, Abler B, Hartmann A, Metzger CD, Walter M. Modulation of attention network activation under antidepressant agents in healthy subjects. Int J Neuropsychopharmacol 2013; 16: 1219-1230.
  • 50 Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001; 98: 6917-1922.
  • 51 Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A 2003; 100: 6186-6191.
  • 52 Farah MJ, Illes J, Cook-Deegan R, Gardner H, Kandel E, King P, Parens E, Sahakian B, Wolpe PR. Neurocognitive enhancement: what can we do and what should we do?. Nat Rev Neurosci 2004; 05: 421-425.
  • 53 Husain M, Mehta MA. Cognitive enhancement by drugs in health and disease. Trends Cogn Sci 2011; 15: 28-36.