Skip to content
Research Article Open access CC BY 3.0

Differential Effects of Anaesthesia on the phMRI Response to Acute Ketamine Challenge

Duncan J. Hodkinson, Carmen de Groote, Shane McKie, J. F. William Deakin, Steve R. Williams

Journal of Advances in Medicine and Medical Research · pp. 373–385 · Published 12 May 2012

10.9734/BJMMR/2012/1412

Abstract

Aims: Pharmacological-challenge magnetic resonance imaging (phMRI) is powerful new tool enabling researchers to map the central effects of neuroactive drugs in vivo. To employ this technique pre-clinically, head movements and the stress of restraint are usually reduced by maintaining animals under general anaesthesia. However, interactions between the drug of interest and the anaesthetic employed may potentially confound data interpretation. NMDA receptor (NMDAR) antagonists used widely to mimic schizophrenia have recently been shown to interact with the anaesthetic halothane. It may be the case that neural and cerebrovascular responses to NMDAR antagonists are dependent on the types of anaesthetic used. Methodology: We compared the phMRI response to NMDAR antagonist ketamine in rats maintained under α-chloralose to those under isoflurane anaesthesia. A randomized placebo/vehicle controlled design was used in each of the anaesthetic groups. Results: Changes in the anaesthetic agent resulted in two very different profiles of activity. In the case of α-chloralose, positive activations in cortical and sub-cortical structures reflected a response which was similar to patterns seen in healthy human volunteers and metabolic maps of conscious rats. However, the use of isoflurane completely reversed such effects, causing widespread deactivations in the cortex and hippocampus. Conclusion: This study provides initial evidence for a drug-anesthetic interaction between ketamine and isoflurane that is very different from responses to α-chloralose-ketamine

Anaesthesia anesthesia NMDA ketamine schizophrenia -chloralose isoflurane phMRI fMRI BOLD rat

References (50)

  1. 1 Region of interest analysis using an SPM toolbox
  2. 2 Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex [DOI]
  3. 3 Glutamate Receptor Dysfunction and Schizophrenia [DOI]
  4. 4 Consciousness and Anesthesia [DOI]
  5. 5 Subanesthetic Doses of Ketamine Stimulate Psychosis in Schizophrenia [DOI]
  6. 6 NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors—implications for models of schizophrenia [DOI]
  7. 7 Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers [DOI]
  8. 8 Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels [DOI]
  9. 9 Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) [DOI]
  10. 10 Comparison of Ketamine-Induced Thought Disorder in Healthy Volunteers and Thought Disorder in Schizophrenia [DOI]
  11. 11 A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: Application to pharmacological MRI [DOI]
  12. 12 Glutamate and the Neural Basis of the Subjective Effects of Ketamine [DOI]
  13. 13 Antipsychotic Drugs [DOI]
  14. 14 Contrasting Synaptic Actions of the Inhalational General Anesthetics Isoflurane and Xenon [DOI]
  15. 15 Effects of Subanesthetic Doses of Ketamine on Regional Cerebral Blood Flow, Oxygen Consumption, and Blood Volume in Humans [DOI]
  16. 16 Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics [DOI]
  17. 17 Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine [DOI]
  18. 18 Neuronal effects of acute citalopram detected by pharmacoMRI [DOI]
  19. 19 Differential Effects of Antipsychotic and Glutamatergic Agents on the phMRI Response to Phencyclidine [DOI]
  20. 20 Functional MRI of apomorphine activation of the basal ganglia in awake rhesus monkeys [DOI]
  21. 21 Clozapine Blunts N-Methyl-d-Aspartate Antagonist-Induced Psychosis: A Study with Ketamine [DOI]
  22. 22 Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane. [DOI]
  23. 23 Pharmacological magnetic resonance imaging: a new application for functional MRI [DOI]
  24. 24 Ketamine Effects on Local Cerebral Blood Flow and Metabolism in the Rat [DOI]
  25. 25 Activation of Metabotropic Glutamate 2/3 Receptors Reverses the Effects of NMDA Receptor Hypofunction on Prefrontal Cortex Unit Activity in Awake Rats [DOI]
  26. 26 Differential effects of clozapine and haloperidol on ketamine-induced brain metabolic activation [DOI]
  27. 27 Cocaine Decreases Cortical Cerebral Blood Flow but Does Not Obscure Regional Activation in Functional Magnetic Resonance Imaging in Human Subjects [DOI]
  28. 28 Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats [DOI]
  29. 29 Effects of Ketamine, MK-801, and Amphetamine on Regional Brain 2-Deoxyglucose Uptake in Freely Moving Mice [DOI]
  30. 30 Mapping the central effects of ketamine in the rat using pharmacological MRI [DOI]
  31. 31 Differential Modulation of Human N-Methyl-d-Aspartate Receptors by Structurally Diverse General Anesthetics [DOI]
  32. 32 Effects of Anesthetics on Mutant N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes [DOI]
  33. 33 A multimodality investigation of cerebral hemodynamics and autoregulation in pharmacological MRI [DOI]
  34. 34 Methodological considerations in rat brain BOLD contrast pharmacological MRI [DOI]
  35. 35 Functional magnetic resonance imaging and c-Fos mapping in rats following an anorectic dose of m-chlorophenylpiperazine [DOI]
  36. 36 Transient blood pressure changes affect the functional magnetic resonance imaging detection of cerebral activation [DOI]
  37. 37 Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat [DOI]
  38. 38 Drug–anaesthetic interaction in phMRI: the case of the psychotomimetic agent phencyclidine [DOI]
  39. 39 Functional magnetic resonance imaging reveals similar brain activity changes in two different animal models of schizophrenia [DOI]
  40. 40 The effects of ketamine on the minimum alveolar concentration of isoflurane in cats [DOI]
  41. 41 Functional magnetic resonance imaging and c‐Fos mapping in rats following a glucoprivic dose of 2‐deoxy‐d‐glucose [DOI]
  42. 42 General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acidA receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium. [DOI]
  43. 43 Characterization of effects of mean arterial blood pressure induced by cocaine and cocaine methiodide on BOLD signals in rat brain [DOI]
  44. 44 Functional magnetic resonance imaging of tonic pain and vasopressor effects in rats [DOI]
  45. 45 Functional imaging of the visual cortex with bold-contrast MRI: Hyperventilation decreases signal response [DOI]
  46. 46 Mapping brain activity following administration of a nicotinic acetylcholine receptor agonist, ABT-594, using functional magnetic resonance imaging in awake rats [DOI]
  47. 47 Contrasting Roles of the N-Methyl-d-Aspartate Receptor in the Production of Immobilization by Conventional and Aromatic Anesthetics [DOI]
  48. 48 Neuroprotective Doses of N-Methyl-D-Aspartate Receptor Antagonists Profoundly Reduce the Minimum Alveolar Anesthetic Concentration (MAC) for Isoflurane in Rats [DOI]
  49. 49 Confounding effects of volatile anesthesia on CBV assessment in rodent forebrain following ethanol challenge [DOI]
  50. 50 Volatile Aromatic Anesthetics Variably Impact Human γ-Aminobutyric Acid Type A Receptor Function [DOI]

Cited by 65

Standardization of Small Animal Imaging—Current Status and Future Prospects

Julia G. Mannheim, Firat Kara, Janine Doorduin · Molecular Imaging and Biology · 2017

Assessment of anesthesia on physiological stability and BOLD signal reliability during visual or acoustic stimulation in the cat

Alexandra T. Levine, Benson Li, Paisley Barnes · Journal of Neuroscience Methods · 2020

Gabapentin‐induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain

B.A. Hooker, G. Tobon, S.J. Baker · European Journal of Pain · 2013

Neuromapping techniques in drug discovery: pharmacological MRI for the assessment of novel antipsychotics

Angelo Bifone, Alessandro Gozzi · Expert Opinion on Drug Discovery · 2012

Neuronal Network Effects of Drug Therapies for CNS Disorders

Carl L. Faingold · Neuronal Networks in Brain Function, CNS Disorders, and Therapeutics · 2014

Modeling the acute pharmacological response to selective serotonin reuptake inhibitors in human brain using simultaneous PET/MR imaging

Gregor Gryglewski, Manfred Klöbl, Neydher Berroterán-Infante · European Neuropsychopharmacology · 2019

Sub-Anesthetic Ketamine Modulates Intrinsic BOLD Connectivity Within the Hippocampal-Prefrontal Circuit in the Rat

Natalia Gass, Adam James Schwarz, Alexander Sartorius · Neuropsychopharmacology · 2013

Differential effect of zoledronic acid on human vascular smooth muscle cells

Hassan Albadawi, Mounir J. Haurani, Rahmi Oklu · Journal of Surgical Research · 2013

Showing 49 of 65 known citations — external sources report more than can currently be individually listed.

Article metrics

Real usage data collected on this platform.

94

Page views

0

PDF downloads

10

Outbound clicks

65

Citations

Views over time

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

Traffic sources

Referring site, by host.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.