Skip to main content

Abstract

Among anaesthetics, ketamine has the distinction of being the only antagonist of N-methyl-D-aspartate (NMDA) receptors approved for clinical use and a potent analgesic with only mild cardiovascular and respiratory depressant properties [1]. Ketamine, however, also has disadvantageous psychomimetic activity, which has been the major factor in limiting ketamine clinical use but also in modelling psychoses in animal and humans [1]. For all these reasons, ketamine has been extensively investigated with neuroimaging techniques.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Reich DL, Silvay G (1989) Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 36: 186–197

    Article  PubMed  CAS  Google Scholar 

  2. Dragunow M, Fault R (1989) The use of c-Fos as a metabolic marker in neuronal pathway tracing. J Neurosci Methods 29: 261–265

    Article  PubMed  CAS  Google Scholar 

  3. Freo U, Ori C (2002) Mapping cerebral metabolic and blood flow effects of general anaesthetics. In: Gullo A (Ed) Anaesthesia Pain Intensive Care Emergency Medicine Vol 17. Springer-Verlag Italia, Milan pp 877–891

    Google Scholar 

  4. Sokoloff I, Reivich M, Kennedy C et al (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization. Theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–916

    Article  PubMed  CAS  Google Scholar 

  5. Sakurada O, Kennedy C, Jehle J et al (1978) Measurements of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol 234:H59–66

    PubMed  CAS  Google Scholar 

  6. Herscovitch P, Markham J, Raichle ME (1983) Brain blood flow measured with intravenous H2 15O. I. Theory and error analysis. J Nucl Med 24: 782–789

    PubMed  CAS  Google Scholar 

  7. Ogawa S, Lee TM, Kay AR et al (1990) Brain magnetic resonance imaging with contrast dependent on blood oxigenation. Proc Nat] Acad Sci USA 87: 9868–9872

    Article  CAS  Google Scholar 

  8. Hartvig P, Valtysson J, Antoni G et al (1994) Brain kinetics of (R)- and (S)-[N-methyl-11C]ketamine in the rhesus monkey studied by positron emission tomography ( PET ). Nucl Med Biol 21: 927–934

    Article  PubMed  CAS  Google Scholar 

  9. Hartvig P, Valtysson J, Lindner KJ et al (1995) Central nervous system effects of subdissociative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers. Clin Pharmacol Ther 58: 165–173

    Article  PubMed  CAS  Google Scholar 

  10. Kumlien E, Hartvig P, Valind S et al (1999) NMDA-receptor activity visualized with (S)-[N-methyl-11C]ketamine and positron emission tomography in patients with medial temporal lobe epilepsy. Epilepsia 40: 30–37

    Article  PubMed  CAS  Google Scholar 

  11. Onoe H, Inoue O, Suzuki K et al (1994) Ketamine increases the striatal N-[11 C] methylspiperone binding in vivo: positron emission tomography study using conscious rhesus monkey. Brain Res 663: 191–198

    Article  PubMed  CAS  Google Scholar 

  12. Kobayashi K, Inoue O, Watanabe Y et al (1995). Difference in response of D2 receptor binding between 11C-N-methylspiperone and 11C-raclopride against anesthetics in rhesus monkey brain. J Neural Transm Gen Sect 100: 147–151

    Article  PubMed  CAS  Google Scholar 

  13. Nader MA, Grant KA, Gage HD et al (1999) PET imaging of dopamine D2 receptors with [18F]fluoroclebopride in monkeys: effects of isoflurane-and ketamine-induced anesthesia. Neuropsychopharmacology 21: 589–596

    Article  PubMed  CAS  Google Scholar 

  14. Tsukada H, Harada N, Nishiyama S et al (2000) Ketamine decreased striatal [(11)C]raclopride binding with no alterations in static dopamine concentrations in the striatal extracellular fluid in the monkey brain: multiparametric PET studies combined with microdialysis analysis. Synapse 37: 95–103

    Article  PubMed  CAS  Google Scholar 

  15. Tsukada H, Nishiyama S, Kakiuchi T et al (2001) Ketamine alters the availability of striatal dopamine transporter as measured by [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the monkey brain. Synapse 42: 273–280

    Article  PubMed  CAS  Google Scholar 

  16. Aalto S, Hirvonen J, Kajander J et al (2002) Ketamine does not decrease striatal dopamine D(2) receptor binding in man. Psychopharmacology 164: 401–406

    Article  PubMed  CAS  Google Scholar 

  17. Kegeles LS, Martinez D, Kochan LD et al (2002) NMDA antagonist effects on striatal dopamine release: positron emission tomography studies in humans. Synapse 43: 19–29

    Article  PubMed  CAS  Google Scholar 

  18. Breier A, Adler CM, Weisenfeld N et al (1998) Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach. Synapse 29: 142–147

    Article  PubMed  CAS  Google Scholar 

  19. Smith GS, Schloesser R, Brodie JD et al (1998) Glutamate modulation of dopamine measured in vivo with positron emission tomography ( PET) and 11C-raclopride in normal human subjects. Neuropsychopharmacology 18: 18–25

    Article  PubMed  CAS  Google Scholar 

  20. Vollenweider FX, Vontobel P, Oye I et al (2000) Effects of (S)-ketamine on striatal dopamine: a [11C]raclopride PET study of a model psychosis in humans. J Psychiatr Res 34: 35–43

    Article  PubMed  CAS  Google Scholar 

  21. Kegeles LS, Abi-Dargham A, Zea-Ponce Y et al (2000) Modulation of amphetamine-induced striatal dopamine release by ketamine in humans: implications for schizophrenia. Biol Psychiatry 48: 627–640

    Article  PubMed  CAS  Google Scholar 

  22. Hassoun W, Le Cavorsin M, Ginovart N et al (2003) PET study of the [(11)C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow. Eur J Nucl Med Mol Imaging 30: 141–148

    Article  PubMed  CAS  Google Scholar 

  23. Dragunow M, Goulding M, Fault RL et al (1990) Induction of c-fos mRNA and protein in neurons and glia after traumatic brain injury: pharmacological characterization. Exp Neurol 107: 236–248

    Article  PubMed  CAS  Google Scholar 

  24. Herrera DG, Robertson HA (1990) N-methyl-D-aspartate receptors mediate activation of the c-fos proto-oncogene in a model of brain injury. Neuroscience 35: 273–281

    Article  PubMed  CAS  Google Scholar 

  25. Herrera DG, Robertson HA (1989) Unilateral induction of c-fos protein in cortex following cortical devascularization. Brain Res 503: 205–213

    Article  PubMed  CAS  Google Scholar 

  26. Szakacs R, Weiczner R, Mihaly A et al (2003) Non-competitive NMDA receptor antagonists moderate seizure-induced c-fos expression in the rat cerebral cortex. Brain Res Bull 59: 485–493

    Article  PubMed  CAS  Google Scholar 

  27. Torres G, Rivier C (1993) Cocaine-induced expression of striatal c-fos in the rat is inhibited by NMDA receptor antagonists. Brain Res Bull 30: 173–176

    Article  PubMed  CAS  Google Scholar 

  28. Abe H, Rusak B, Robertson HA (1992) NMDA and non-NMDA receptor antagonists inhibit photic induction of fos protein in the hamster suprachiasmatic nucleus. Brain Res Bull 28: 831–835

    Article  PubMed  CAS  Google Scholar 

  29. Nishizawa N, Nakao S, Nagata A et al (2000) The effect of ketamine isomers on both mice behavioral responses and c-fos expression in the posterior cingulate and retrosplenial cortices. Brain Res 857: 188–192

    Article  PubMed  CAS  Google Scholar 

  30. Nakao S, Nagata A, Miyamoto E (2003) Inhibitory effect of propofol on ketamine-induced c-fos expression in the rat posterior cingulate and retrosplenial cortices is mediated by GABAA receptor activation. Acta Anaesthesiol Scand 47: 284–290

    Article  PubMed  CAS  Google Scholar 

  31. Benthuysen JL, Hance AJ, Quam DD et al (1989) Comparison of isomers of ketamine on catalepsy in the rat and electrical activity of the brain and behaviour in the cat. Neuropharmacology 28: 1003–1009

    Article  PubMed  CAS  Google Scholar 

  32. Marietta MP, Way WL, Castagnoli N Jr et al (1977) On the pharmacology of the ketamine enantiomorphs in the rat. J Pharmacol Exp Ther 202: 157–165

    PubMed  CAS  Google Scholar 

  33. Bowers MB Jr, Hoffman FJ Jr (1984) Homovanillic acid in rat caudate and prefrontal cortex following phencyclidine and amphetamine. Psychopharmacology 84: 136–137

    Article  PubMed  CAS  Google Scholar 

  34. Nagata A, Nakao Si S, Nishizawa N et al (2001) Xenon inhibits but N(2)O enhances ketamineinduced c-fos expression in the rat posterior cingulate and retrosplenial cortices. Anesth Analg 92: 362–368

    Article  PubMed  CAS  Google Scholar 

  35. Nakao S, Miyamoto E, Masuzawa M et al (2002) Ketamine-induced c-fos expression in the mouse posterior cingulate and retrosplenial cortices is mediated not only via NMDA receptors but also via sigma receptors. Brain Res 926: 191–196

    Article  PubMed  CAS  Google Scholar 

  36. Nakao S, Adachi T, Murakawa M et al (1996) Halothane and diazepam inhibit ketamine-induced c-fos expression in the rat cingulate cortex. Anesthesiology 85: 874–882

    Article  PubMed  CAS  Google Scholar 

  37. Nagata A, Nakao S, Miyamoto E et al (1998) Propofol inhibits ketamine-induced c-fos expression in the rat posterior cingulate cortex. Anesth Analg 87: 1416–1420

    PubMed  CAS  Google Scholar 

  38. Nelson LE, Guo TZ, Lu J et al (2002) The sedative component of anesthesia is mediated by GABA(A) receptors in an endogenous sleep pathway. Nat Neurosci 5: 979–984

    Article  PubMed  CAS  Google Scholar 

  39. Ma D, Wilhelm S, Maze M, Franks NP (2002) Neuroprotective and neurotoxic properties of the ‘inert’ gas, xenon. Br J Anaesth 89: 739–746

    Article  PubMed  CAS  Google Scholar 

  40. Davis DW, Mans AM, Biebuyck JF, Hawkins RA (1988) The influence of ketamine on regional brain glucose use. Anesthesiology 69: 199–205

    Article  PubMed  CAS  Google Scholar 

  41. Duncan GE, Miyamoto S, Leipzig JN, Lieberman JA (1999) Comparison of brain metabolic activity patterns induced by ketamine, MK-801 and amphetamine in rats: support for NMDA receptor involvement in responses to subanesthetic dose of ketamine. Brain Res 843: 171–183

    Article  PubMed  CAS  Google Scholar 

  42. Eintrei C, Sokoloff L, Smith CB (1999) Effects of diazepam and ketamine administered individually or in combination on regional rates of glucose utilization in rat brain. Br J Anaesth 82: 596–602

    Article  PubMed  CAS  Google Scholar 

  43. Miyamoto S, Leipzig JN, Lieberman JA, Duncan GE (2000) Effects of ketamine, MK-801, and amphetamine on regional brain 2-deoxyglucose uptake in freely moving mice. Neuropsychopharmacology 22: 400–412

    Article  PubMed  CAS  Google Scholar 

  44. Nelson SR, Howard RB, Cross RS, Samson F (1980) Ketamine-induced changes in regional glucose utilization in the rat brain. Anesthesiology 52: 330–334

    Article  PubMed  CAS  Google Scholar 

  45. Crosby G, Crane AM, Sokoloff L (1982) Local changes in cerebral glucose utilization during ketamine anesthesia. Anesthesiology 56: 437–443

    Article  PubMed  CAS  Google Scholar 

  46. Hammer RP Jr, Herkenham M (1983) Altered metabolic activity in the cerebral cortex of rats exposed to ketamine. J Comp Neurol 220: 396–404

    Article  PubMed  CAS  Google Scholar 

  47. Schwedler M, Miletich DJ, Albrecht RF (1982) Cerebral blood flow and metabolism following ketamine administration. Can Anaesth Soc J 29: 222–226

    Article  PubMed  CAS  Google Scholar 

  48. Oren RE, Rasool NA, Rubinstein EH (1982) Effect of ketamine on cerebral cortical blood flow and metabolism in rabbits. Stroke 18: 441–444

    Article  Google Scholar 

  49. Chi OZ, Wei HM, Klein SL, Weiss HR (1994) Effect of ketamine on heterogeneity of cerebral microregional venous 02 saturation in the rat. Anesth Analg 79: 860–866

    Article  PubMed  CAS  Google Scholar 

  50. Cavazzuti M, Porro CA, Biral GP et al (1987) Ketamine effects on local cerebral blood flow and metabolism in the rat. J Cereb Blood Flow Metab 7: 806–811

    Article  PubMed  CAS  Google Scholar 

  51. Lei H, Grinberg O, Nwaigwe CI et al (2001) The effects of ketamine-xylazine anesthesia on cerebral blood flow and oxygenation observed using nuclear magnetic resonance perfusion imaging and electron paramagnetic resonance oximetry. Brain Res 913: 174–179

    Article  PubMed  CAS  Google Scholar 

  52. Burdett NG, Menon DK, Carpenter TA et al (1995) Visualisation of changes in regional cerebral blood flow (rCBF) produced by ketamine using long TE gradient-echo sequences: preliminary results. Magn Reson Imaging 13: 549–553

    Article  PubMed  CAS  Google Scholar 

  53. Mayberg TS, Lam AM, Matta BF et al (1995) Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesth Analg 81: 84–89

    PubMed  CAS  Google Scholar 

  54. Strebel S, Kaufmann M, Maitre L, Schaefer HG (1995) Effects of ketamine on cerebral blood flow velocity in humans. Influence of pretreatment with midazolam or esmolol. Anaesthesia 50: 223–228

    Article  PubMed  CAS  Google Scholar 

  55. Leopold DA, Plettenberg HK, Logothetis NK (2002) Visual processing in the ketamine-anesthetized monkey. Optokinetic and blood oxygenation level-dependent responses. Exp Brain Res 143: 359–372

    Article  PubMed  CAS  Google Scholar 

  56. Oguchi K, Arakawa K, Nelson SR, Samson F (1982) The influence of droperidol, diazepam, and physostigmine on ketamine-induced behavior and brain regional glucose utilization in rat. Anesthesiology 57: 353–358

    Article  PubMed  CAS  Google Scholar 

  57. Miyamoto S, Mailman RB, Lieberman JA, Duncan GE (2001) Blunted brain metabolic response to ketamine in mice lacking D(1A) dopamine receptors. Brain Res 894: 167–180

    Article  PubMed  CAS  Google Scholar 

  58. Duncan GE, Leipzig JN, Mailman RB, Lieberman JA (1998) Differential effects of clozapine and haloperidol on ketamine-induced brain metabolic activation. Brain Res 812: 65–75

    Article  PubMed  CAS  Google Scholar 

  59. Duncan GE, Miyamoto S, Leipzig JN, Lieberman JA (2000) Comparison of the effects of clozapine, risperidone, and olanzapine on ketamine-induced alterations in regional brain metabolism. J Pharmacol Exp Ther 293: 8–14

    PubMed  CAS  Google Scholar 

  60. Duncan GE, Miyamoto S, Lieberman JA (2003) Chronic administration of haloperidol and olanzapine attenuates ketamine-induced brain metabolic activation. J Pharmacol Exp Ther 305: 999–1005

    Article  PubMed  CAS  Google Scholar 

  61. Breier A, Malhotra AK, Pinals DA et al (1997) Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers. Am J Psychiatry 154: 805–811

    PubMed  CAS  Google Scholar 

  62. Vollenweider FX, Leenders KL, Oye I et al (1997) Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography ( PET ). Eur Neuropsychopharmacol 7: 25–38

    Article  PubMed  CAS  Google Scholar 

  63. Holcomb HH, Lahti AC, Medoff DR et al (2001) Sequential regional cerebral blood flow brain scans using PET with H2(15)0 demonstrate ketamine actions in CNS dynamically. Neuropsychopharmacology 25: 165–172

    Article  PubMed  CAS  Google Scholar 

  64. Vollenweider FX, Leenders KL, Scharfetter C et al (1997) Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose ( FDG ). Eur Neuropsychopharmacol 7: 9–24

    Article  CAS  Google Scholar 

  65. Beason-Held L, Holcomb H, Tamminga C (2003) Cognition and brain function: the effects of ketamine and nicotine in healthy subjects (abstract). Neuroimage, Human Brain Mapping 2003 Meeting, abstract 140

    Google Scholar 

  66. Abel KM, Allin MP, Kucharska-Pietura K et al (2203) Ketamine and fMRI BOLD signal: distinguishing between effects mediated by change in blood flow versus change in cognitive state. Hum Brain Mapp 18: 135–145

    Article  Google Scholar 

  67. Honey G, Honey R, Sharar S et al (2003) Investigation of the effects of low dose ketamine on episodic memory encoding using fMRI (abstract). Neuroimage, Human Brain Mapping 2003 Meeting, abstract 242

    Google Scholar 

  68. Honey G, Honey R, Sharar S et al (2003) Investigation on the effects of low dose ketamine on episodic memory retrieval using fMRI (abstract). Neuroimage, Human Brain Mapping 2003 Meeting, abstract 170

    Google Scholar 

  69. Fu C, Abel K, Alen M, Vythelingum G et al (2003) `K’ is for ketamine or knot, neural correlates of a ketamine-induced psychotic state on verbal fluency (abstract). Neuroimage, Human Brain Mapping 2003 Meeting, abstract 1286

    Google Scholar 

  70. O’Loughlin CJ. Sharar RS. Honey G et al (2003) Investigating the effects of ketamine in a continuous performance task using fMRI (abstract). Neuroimage, Human Brain Mapping 2003 Meeting, abstract 494

    Google Scholar 

  71. Abel KM, Allin MP, Kucharska-Pietura K et al (2003) Ketamine alters neural processing of facial emotion recognition in healthy men: an fMR1 study. Neuroreport 14: 387–391

    Article  PubMed  CAS  Google Scholar 

  72. Medoff DR, Holcomb HH, Lahti AC, Tamminga CA (2001) Probing the human hippocampus using rCBF: contrasts in schizophrenia. Hippocampus 11: 543–550

    Article  PubMed  CAS  Google Scholar 

  73. Lahti AC, Holcomb HH, Medoff DR. Tamminga CA (1995) Ketamine activates psychosis and alters limbic blood flow in schizophrenia. Neuroreport 6:869–872

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Italia, Milano

About this paper

Cite this paper

Freo, U., Ori, C. (2004). Neuroimaging studies on ketamine. In: Gullo, A. (eds) Anaesthesia, Pain, Intensive Care and Emergency Medicine — A.P.I.C.E.. Springer, Milano. https://doi.org/10.1007/978-88-470-2189-1_18

Download citation

  • DOI: https://doi.org/10.1007/978-88-470-2189-1_18

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-0235-7

  • Online ISBN: 978-88-470-2189-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics