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The effect of the muscarinic antagonist scopolamine on regional cerebral blood flow during the performance of a memory task

Abstract

Scopolamine, a muscarinic antagonist, impairs memory performance in both humans and animals. In this study, repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers whilst performing auditory verbal memory tasks, before and after the administration of scopolamine (0.4 mg s.c.) or placebo. Compared to placebo, scopolamine increased blood flow in the lateral occipital cortex bilaterally and the left orbitofrontal region. Scopolamine decreased rCBF in the region of the right thalamus, the precuneus and the right and left lateral premotor areas. Scopolamine attenuated memory-task-induced increases of rCBF in the left and right prefrontal cortex and the right anterior cingulate region. These data suggest that acute blockade of cholinergic neurotransmission affects diverse brain areas, including components of the visual and motor systems, and, in addition, modulates memory task activations at distinct points in a distributed network for memory function.

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References

  1. Bailey DL, Jones T, Friston KJ, Colebatch JG, Frackowiak RSJ (1991) Physical validation of statistical parametric mapping. J Cereb Blood Flow Metab 11 [suppl 2]: S150

  2. Bajalan AAA, Wright CE, Van Der Vleit VJ (1986) Changes in the human visual evoked potential caused by the anticholinergic agent hyoscine hydrobromide: comparison with results from Alzheimer's disease. J Neurol Neurosurg Psychiatry 49: 175–182

  3. Baron JC, D'Antona R, Pantano P, Serder M, Samson Y, Bousser MG (1986) Effects of thalamic stroke on energy metabolism of the cerebral cortex. Brain 109: 1243–1259

  4. Bench CJ, Frith CD, Grasby PM, Friston KJ, Paulesu E, Frackowiak RSJ, Dolan RJ (1993) Investigations of the functional anatomy of attention using the stroop test. Neuropsychologia 31: 907–922

  5. Blin J, Ray CA, Piercey MF, Bartko JJ, Mouradian MM, Chase TN (1994) Comparison of cholinergic drug effects on regional brain glucose consumption in rats and humans by means of autoradiography and positron emission tromography. Brain Res 635: 196–202

  6. Burnstock G (1980) Cholinergic and purinergic regulation of blood vessels. In: Bohr DF, Somolyo AP, Sparks HV (eds) Handbook of physiology, sect 2, The cardiovascular system, vol 2. American Physiological Society, Bethesda, pp 567–612

  7. Bymaster FP, Heath I, Hendrix JC, Shannon HE (1993) Comparative behavioural and neurochemical activities of cholinergic antagonists in rats. J Pharmacol Exp Ther 267: 16–24

  8. Calne DB (1978) Parkinsonism, clinical and neuropharmacologic aspects. Postgrad Med 64: 82–88

  9. Cedarbaum JM, Schleifer LS (1990) Drugs for Parkinson's disease, spasticity and acute muscle spasms. In: Goodman Gilman A, Rall TW, Nies AS, Taylor P (eds) Goodman and Gilman's The pharmacologic basis of therapeutics. Pergamon Press, New York, pp 463–484

  10. Collerton D (1987) Problems in the cognitive neurochemistry of Alzheimer's disease. In: Stahl SM, Iversen SD, Goodman EC (eds) Cognitive neurochemistry. Oxford University Press, Oxford, pp 272–302

  11. Crow TJ, Grove-White IG (1973) An analysis of the learning deficit following hyoscine administration to man. Br J Pharmacol 49: 322–327

  12. Crowell EB, Ketchum JS (1967) The treatment of scopolamine-induced delirium with physostigmine. Clin Pharmacol Ther 8: 409–414

  13. Dewey SL, Smith GS, Logan J, Bridie JD, Simkowitz P, MacGregor RR, Fowler JS, Volkow ND, Wolf AP (1993) Effects of central cholinergic blockade on striatal dopamine release measured with positron emission tomography in normal human subjects. Proc Natl Acad Sci USA 90: 11816–11820

  14. Drachman DA, Leavitt J (1974) Human memory and the cholinergic system. Arch Neurol 30: 113–121

  15. Edvinsson L, MacKenzie ET, McCulloch J (1993) Acetylcholine. In: Edvinsson L, MacKenzie ET, McCulloch J (eds) Cerebral blood flow and metabolism. Raven Press, New York, pp 285–312

  16. Fox PT, Mintun MA (1989) Non-invasive functional brain mapping by change distribution analysis of averaged PET images of H2 15O tissue activity. J Nucl Med 30: 141–149

  17. Friston KJ, Passingham RE, Nutt JG, Heather JD, Sawle GV, Frackowiak RSJ (1989) Localization in PET images: direct fitting of the intercommissural (AC-PC) line. J Cereb Blood Flow Metab 9: 690–695

  18. Friston KJ, Frith CD, Liddle PF, Lammertsma AA, Dolan RJ, Frackowiak RSJ (1990) The relationship between local and global changes in PET scans. J Cereb Blood Flow Metab 10: 458–466

  19. Friston KJ, Frith CD, Liddle PF, Frackowiak RSJ (1991a) Plastic transformation of PET images. J Comput Assist Tomogr 15: 634–639

  20. Friston KJ, Frith CD, Liddle PF, Frackowiak RSJ (1991b) Comparing functional (PET) images: the assessment of significant change. J Cereb Blood Flow Metab 11: 690–699

  21. Friston KJ, Grasby PM, Bench C, Frith CD, Cowen PJ, Liddle PF, Frackowiak RSJ, Dolan RJ (1992) Measuring the neuromodulatory effects of drugs in man with positron emission tomography. Neurosci Lett 141: 106–110

  22. Grasby PM, Friston KJ, Bench CJ, Frith CD, Paulesu E, Cowen PJ, Liddle PF, Frackowiak RSJ, Dolan RJ (1992) The effect of apomorphine and buspirone on regional cerebral blood flow during the performance of a cognitive task — measuring neuromodulatory effects of psychotropic drugs in man. Eur J Neurosci 4: 1203–1212

  23. Grasby PM, Frith CD, Friston KJ, Bench C, Frackowiak RSJ, Dolan RJ (1993) Functional mapping of brain areas implicated in auditory-verbal memory function. Brain 116: 1–20

  24. Hand DJ, Taylor CC (1991) Multivariate analysis of variance and repeated measures. Chapman and Hall, London, pp 9–44

  25. Heller-Brown J (1990) Atropine, scopolamine and related antimuscarinic drugs. In: Goodman Gilman A, Rall TW, Nies AS, Taylor P (eds) Goodman and Gilmans The pharmacologic basis of therapeutics. Pergamon Press, New York, pp 150–165

  26. Honer WG, Prohovnik I, Smith G, Lucas LR (1988) Scopolamine reduces frontal cortex perfusion. J Cereb Blood Flow Metabol 8: 635–641

  27. Kemel ML, Desban M, Glowinski J, Gauchy C (1992) Functional heterogenity of the matrix compartment in the cat caudate nucleus as demonstrated by the cholinergic presynaptic regulation of dopamine release. Neuroscience 50: 597–610

  28. Ketchum JS, Sidell FR, Crowell EB, Aghajanian GK, Haines AH (1973) Atropine, scopolamine and ditran: comparative pharmacology and antagonists in man. Psychopharmacologia 28: 121–145

  29. Kopelman MD (1987) How far could cholinergic depletion account for the memory deficits of Alzheimer-type dementia or the alcoholic Korsakoff syndrome. In: Stahl SM, Iversen SD, Goodman EC (eds) Cognitive neurochemistry. Oxford University Press, Oxford, pp 303–326

  30. Lammertsma AA, Cunningham VJ, Deiber MP, Heather JD, Bloomfield PM, Nutt JG, Frackowiak RSJ, Jones T (1990) Combination of dynamic and integral methods for generating reproducible functional CBF images. J Cereb Blood Flow Metabol 10: 675–686

  31. Lang AE (1989) Drug treatment of dystonia. In: Quinn NP, Jenner PG (eds) Disorders of movement: clinical, pharmacological and physiological aspects. Academic Press, London, pp 315–317

  32. Leigh PN (1989) Functional organization of the basal ganglia. In: Quinn NP, Jenner PG (eds) Disorders of movement: clinical, pharmacological and physiological aspects. Academic Press, London, pp 18–19

  33. Mackay C, Cox T, Burrows G, Lazzerini T (1978) An inventory for the measurement of self-reported stress and arousal. Br J Soc Clin Psychol 17: 283–284

  34. Maquet P, Dive D, Salmon E, Sadzot B, Franco G, Poirrier R, von Frenckell R, Franck G (1990) Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluro-2-deoxy-d-glucose method. Brain Res 513: 136–143

  35. Mazziotta JC, Huang SC, Phelps ME, Carson RE, MacDonalds NS, Mahoney K (1985) A non-invasive positron computed tomography technique using oxygen-15 labelled water for the evaluation of neurobehavioural task batteries. J Cereb Blood Flow Metab 5: 70–78

  36. McCulloch J (1982) Mapping functional alterations in the CNS with [14C]-deoxyglucose. In: Iversen LI, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology. Plenum, New York, pp 321–410

  37. McGeer PL, Eccles JC, McGeer EG (1987) Cholinergic Neurons. In: McGeer PL, Eccles JC, McGeer EG (eds) Molecular neurobiology of the mammalian brain. Plenum, New York, pp 237–263

  38. Pardo JV, Pardo PJ, Janer KW, Raichle ME (1990) The anterior cingulate cortex mediates processing selection in the stroop attentional conflict paradigm. Proc Natl Acad Sci USA 87: 256–259

  39. Passingham R (1993) The frontal lobes and voluntary action. Oxford University Press, Oxford, pp 38–68

  40. Posner MI, Petersen SE, Fox PT, Raichle ME (1988) Localization of cognitive operations in the human brain. Science 240: 1627–1631

  41. Quinlan P T (1992) The Oxford psycholinguistic database. Oxford University Press, Oxford

  42. Raichle ME (1987) Circulatory and metabolic correlations of brain function in normal humans. In: Plum F (eds) Handbook of physiology, sect 1. The nervous system, vol 5: higher functions of the brain. Oxford University Press, New York, pp 643–674

  43. Ramsay SC, Murphy K, Shea SA, Friston KJ, Lammertsma AA, Clark JC, Adams L, Guz A, Frackowiak RSJ (1993) Changes in global cerebral blood flow in humans: effect on regional cerebral blood flow during a neural activation task. J Physiol (Lond) 471: 521–534

  44. Ray CA, Blin J, Chase TN, Piercey MF (1992) Effects of cholinergic agonists on regional brain energy metabolism in the scopolamine-treated rat. Neuropharmacology 31: 1193–1199

  45. Robb RA (1990) A software system for interactive and quantitative analysis of biomedical images. In: Hohne KH, Fuchs H, Pizer SM (eds) 3D Imaging in Medicine. NATO ASI Series, Springer, London

  46. Rolls ET, Treves A (1990) The relative advantage of sparse versus distributed encoding for associative neuronal networks in the brain. Network 1: 407–421

  47. Rusted J (1994) Cholinergic blockade and human information processing: are we asking the right questions? J Psychopharmacol 8: 54–59

  48. Sahakian BJ (1988) Cholinergic drugs and human cognitive performance. In: Iversen LI, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology. Plenum, New York, pp 393–424

  49. Shallice T, Fletcher P, Frith CD, Grasby P, Frackowiak RSJ, Dolan RJ (1994) The brain regions associated with the acquisition and retrieval of verbal episodic memory. Nature 368: 633–635

  50. Shimamura AP, Janowsky JS, Squire LR (1991) What is the role of frontal lobe damage in memory disorders? In: Levin HS, Eisenberg HM, Benton AL (eds) Frontal lobe function and dysfunction. Oxford University Press, New York, pp 173–195

  51. Soncrant TT, Pizzolato G, Battistin L (1986) The use of drugs as probes of cerebral function. In: Battistin L, Gerstenbrand F (eds) PET and NMR: new perspectives in neuroimaging and in clinical neurochemistry. Liss, New York, pp 131–149

  52. Spinks TJ, Jones T, Gilardi MC, Heather JD (1988) Physical performance of the latest generation of commercial positron scanner. IEEE Trans Nucl Sci 35: 721–725

  53. Squire LR, Zola-Morgan S (1991) The medial temporal lobe memory system. Science 253: 1380–1386

  54. Steriade M, McCarley RW (1990) Brainstem control of wakefulness and sleep. Plenum Press, New York, pp 164–185

  55. Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262: 679–685

  56. Talairach J, Tournoux P (1988) A co-planar stereotactic atlas of a human brain. Thieme, Stuttgart

  57. Tulving E, Kapur S, Craik FIM, Moscovitch M, Houle S (1994) Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. Proc Natl Acad Sci USA 91: 2016–2020

  58. Watson JDG, Myers R, Frackowiak RSJ, Hajnal JV, Woods RP, Mazziotta JC, Shipp S, Zeki S (1993) Area V5 of the human brain: evidence from a combined study using positron emission tomography and magnetic resonance imaging. Cereb Cortex 3: 79–94

  59. Wildt AR, Ahtola OT (1978) Analysis of covariance. (University papers: Quantitative applications in the social sciences ser no. 12). Sage Publications, Beverly Hills, California

  60. Woods RP, Cherry SR, Mazziotta JC (1992) A rapid automated algorithm for accurately aligning and reslicing positron emission tomography images. J Comput Assist Tomogr 16: 620–633

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Grasby, P.M., Frith, C.D., Paulesu, E. et al. The effect of the muscarinic antagonist scopolamine on regional cerebral blood flow during the performance of a memory task. Exp Brain Res 104, 337–348 (1995). https://doi.org/10.1007/BF00242019

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Key words

  • Scopolamine
  • Memory
  • Positron emission tomography
  • Human