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Mapping the central effects of ketamine in the rat using pharmacological MRI

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An Erratum to this article was published on 29 August 2006

Abstract

Rationale

Ketamine induces, in both humans and rodents, behaviours analogous to some of the symptoms of schizophrenia.

Objectives

To utilise pharmacological magnetic resonance imaging (phMRI) techniques that identify changes in blood-oxygenation-level-dependent (BOLD) contrast to determine the temporal and spatial neuronal activation profile of ketamine in the rat brain.

Method

To obtain a pharmacodynamic profile of the drug, we assessed changes in locomotor activity after vehicle and 10 and 25 mg/kg ketamine. Separate animals were then anaesthetised and placed in a 4.7-T magnetic resonance (MR) system before receiving the same doses of ketamine during serial MR image acquisition. Subsequent statistical parametric mapping of the main effect of the drug was then undertaken to identify changes in BOLD contrast. Levels of γ-aminobutyric acid (GABA) and dopamine (DA) in brain areas showing localised changes in BOLD contrast were then assessed via microdialysis.

Results

Both doses of ketamine produced increases in BOLD image contrast in frontal, hippocampal, cortical and limbic areas. A further investigation of the release of DA and its metabolites in the nucleus accumbens, both in anaesthesised and freely moving rats, corroborated these findings. However, an investigation of GABA and DA levels in the ventral pallidum gave no indication of changes in activity.

Conclusions

Ketamine produced localised dose-dependent alterations in BOLD MR signal, which correlate with the pharmacodynamic profile of the drug. These results can be, at least, partially substantiated with complementary techniques but consideration must be given to the input function applied to the MR signal and the use of anaesthesia during phMRI experimentation.

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References

  • Adams B, Moghaddam B (1998) Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine. J Neurosci 18:5545–5554

    CAS  PubMed  Google Scholar 

  • Akeson J, Bjorkman S, Messeter K, Rosen I, Helfer M (1993) Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig. Acta Anaesthesiol Scand 37:211–218

    Article  CAS  PubMed  Google Scholar 

  • Albanese J, Arnaud S, Rey M, Thomachot L, Alliez B, Martin C (1997) Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology 87:1328–1334

    Article  CAS  PubMed  Google Scholar 

  • Anis NA, Berry SC, Burton NR, Lodge D (1983) The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 79:565–575

    CAS  PubMed  Google Scholar 

  • Bandettini PA, Wong EC, Hinks RS, Tikofsky RS, Hyde JS (1992) Time course EPI of human brain function during task activation. Magn Reson Med 25:390–397

    Article  CAS  PubMed  Google Scholar 

  • Beckmann CF (2002) Probabilistic independant components analysis for fMRI. FMRIB Analysis Group

  • Berg-Johnsen J, Langmoen IA (1992) The effect of isoflurane on excitatory synaptic transmission in the rat hippocampus. Acta Anaesthesiol Scand 36:350–355

    Article  CAS  PubMed  Google Scholar 

  • Breier A, Malhotra AK, Pinals DA, Weisenfeld NI, Pickar D (1997) Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers. Am J Psychiatr 154:805–811

    CAS  PubMed  Google Scholar 

  • Brett M, Anton J-L, Valabreque R, Poline J-P (2002) Region of interest analysis using an SPM toolbox. Abstract presented at the 8th international conference on functional mapping of the human brain, June 2–6, 2002, Sendai, Japan. Neuroimage 16:2

    Google Scholar 

  • Bristow LJ, Hutson PH, Thorn L, Tricklebank MD (1993) The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents. Br J Pharmacol 108:1156–1163

    CAS  PubMed  Google Scholar 

  • Burdett NG, Menon DK, Carpenter TA, Jones JG, Hall LD (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  CAS  PubMed  Google Scholar 

  • Carboni E, Imperato A, Perezzani L, Di Chiara G (1989) Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of freely moving rats. Neuroscience 28:653–661

    Article  CAS  PubMed  Google Scholar 

  • Cash D, Read SJ, Lythgoe D, Williams SCR, Roberts TJ, Ireland MD, Smart SC, Hunter AJ (2003) Autoradiographic and functional MRI assessment of rat brain response to amphetamine under halothane and a-chloralose anaesthesia. J Cereb Blood Flow Metab 23:S10

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Chambers RA, Krystal JH, Self DW (2001) A neurobiological basis for substance abuse comorbidity in schizophrenia. Biol Psychiatry 50:71–83

    Article  CAS  PubMed  Google Scholar 

  • Chen YC, Choi JK, Andersen SL, Rosen BR, Jenkins BG (2004) Mapping dopamine D2/D3 receptor function using pharmacological magnetic resonance imaging. Psychopharmacology (Berl) 180(4):705–715

    Article  CAS  Google Scholar 

  • Chen YI, Choi JK, Jenkins BG (2005) Mapping interactions between dopamine and adenosine A2a receptors using pharmacologic MRI. Synapse 55:80–88

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Dawson B, Michenfelder JD, Theye RA (1971) Effects of ketamine on canine cerebral blood flow and metabolism: modification by prior administration of thiopental. Anesth Analg 50:443–447

    Article  CAS  PubMed  Google Scholar 

  • de Sousa SL, Dickinson R, Lieb WR, Franks NP (2000) Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon. Anesthesiology 92:1055–1066

    Article  PubMed  Google Scholar 

  • Dixon AL, Prior M, Morris PM, Shah YB, Joseph MH, Young AM (2005) Dopamine antagonist modulation of amphetamine response as detected using pharmacological MRI. Neuropharmacology 48:236–245

    Article  CAS  PubMed  Google Scholar 

  • Duncan GE, Moy SS, Knapp DJ, Mueller RA, Breese GR (1998) Metabolic mapping of the rat brain after subanesthetic doses of ketamine: potential relevance to schizophrenia. Brain Res 787:181–190

    Article  CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Ellison G (1995) The N-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias. Brain Res Brain Res Rev 20:250–267

    Article  CAS  PubMed  Google Scholar 

  • Friston KJ, Holmes AP, Worsley KJ, Poline JP, Frith CD, Frackowiak RSJ (1995) Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 2:189–210

    Article  Google Scholar 

  • Grace AA (2000) Gating of information flow within the limbic system and the pathophysiology of schizophrenia. Brain Res Brain Res Rev 31:330–341

    Article  CAS  PubMed  Google Scholar 

  • Harel N, Lee SP, Nagaoka T, Kim DS, Kim SG (2002) Origin of negative blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow Metab 22:908–917

    Article  PubMed  Google Scholar 

  • Hetzler BE, Wautlet BS (1985) Ketamine-induced locomotion in rats in an open-field. Pharmacol Biochem Behav 22:653–655

    Article  CAS  PubMed  Google Scholar 

  • Hewitt KN, Shah YB, Prior MJ, Morris PG, Hollis CP, Fone KC, Marsden CA (2005) Behavioural and pharmacological magnetic resonance imaging assessment of the effects of methylphenidate in a potential new rat model of attention deficit hyperactivity disorder. Psychopharmacology (Berl) 180(4):716–723

    Article  CAS  Google Scholar 

  • Hirota K, Okawa H, Appadu BL, Grandy DK, Devi LA, Lambert DG (1999) Stereoselective interaction of ketamine with recombinant mu, kappa, and delta opioid receptors expressed in Chinese hamster ovary cells. Anesthesiology 90:174–182

    Article  CAS  PubMed  Google Scholar 

  • Hlustik P, Noll DC, Small SL (1998) Suppression of vascular artifacts in functional magnetic resonance images using MR angiograms. Neuroimage 7:224–231

    Article  CAS  PubMed  Google Scholar 

  • Houston GC, Papadakis NG, Carpenter TA, Hall LD, Mukherjee B, James MF, Huang CL (2001) Mapping of brain activation in response to pharmacological agents using fMRI in the rat. Magn Reson Imaging 19:905–919

    Article  CAS  PubMed  Google Scholar 

  • Hunt MJ, Kessal K, Garcia R (2005) Ketamine induces dopamine-dependent depression of evoked hippocampal activity in the nucleus accumbens in freely moving rats. J Neurosci 25:524–531

    Article  CAS  PubMed  Google Scholar 

  • Hustveit O, Maurset A, Oye I (1995) Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacol Toxicol 77:355–359

    Article  CAS  PubMed  Google Scholar 

  • Imperato A, Scrocco MG, Bacchi S, Angelucci L (1990) NMDA receptors and in vivo dopamine release in the nucleus accumbens and caudatus. Eur J Pharmacol 187:555–556

    Article  CAS  PubMed  Google Scholar 

  • Ireland MD, Lowe AS, Reavill C, James MF, Leslie RA, Williams SC (2005) Mapping the effects of the selective dopamine D2/D3 receptor agonist quinelorane using pharmacological magnetic resonance imaging. Neuroscience 133:315–326

    Article  CAS  PubMed  Google Scholar 

  • Irifune M, Fukuda T, Nomoto M, Sato T, Kamata Y, Nishikawa T, Mietani W, Yokoyama K, Sugiyama K, Kawahara M (1997) Effects of ketamine on dopamine metabolism during anesthesia in discrete brain regions in mice: comparison with the effects during the recovery and subanesthetic phases. Brain Res 763:281–284

    Article  CAS  PubMed  Google Scholar 

  • Irifune M, Sato T, Kamata Y, Nishikawa T, Dohi T, Kawahara M (2000) Evidence for GABA(A) receptor agonistic properties of ketamine: convulsive and anesthetic behavioral models in mice. Anesth Analg 91:230–236

    Article  CAS  PubMed  Google Scholar 

  • Irifune M, Shimizu T, Nomoto M (1991) Ketamine-induced hyperlocomotion associated with alteration of presynaptic components of dopamine neurons in the nucleus accumbens of mice. Pharmacol Biochem Behav 40:399–407

    Article  CAS  PubMed  Google Scholar 

  • Jevtovic-Todorovic V, Todorovic SM, Mennerick S, Powell S, Dikranian K, Benshoff N, Zorumski CF, Olney JW (1998) Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 4:460–463

    Article  CAS  PubMed  Google Scholar 

  • Jones N, O’Neill MJ, Tricklebank M, Libri V, Williams SC (2005) Examining the neural targets of the AMPA receptor potentiator LY404187 in the rat brain using pharmacological magnetic resonance imaging. Psychopharmacology (Berl) 180(4):743–751

    Article  CAS  Google Scholar 

  • Kalisch R, Elbel GK, Gossl C, Czisch M, Auer DP (2001) Blood pressure changes induced by arterial blood withdrawal influence bold signal in anesthesized rats at 7 Tesla: implications for pharmacologic MRI. Neuroimage 14:891–898

    Article  CAS  PubMed  Google Scholar 

  • Kapur S, Seeman P (2002) NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia. Mol Psychiatry 7:837–844

    Article  CAS  PubMed  Google Scholar 

  • Keilhoff G, Becker A, Grecksch G, Wolf G, Bernstein HG (2004) Repeated application of ketamine to rats induces changes in the hippocampal expression of parvalbumin, neuronal nitric oxide synthase and cFOS similar to those found in human schizophrenia. Neuroscience 126:591–598

    Article  CAS  PubMed  Google Scholar 

  • Kretschmer BD (2000) NMDA receptor antagonist-induced dopamine release in the ventral pallidum does not correlate with motor activation. Brain Res 859:147–156

    Article  CAS  PubMed  Google Scholar 

  • Krimer LS, Muly EC 3rd, Williams GV, Goldman-Rakic PS (1998) Dopaminergic regulation of cerebral cortical microcirculation. Nat Neurosci 1:286–289

    Article  CAS  PubMed  Google Scholar 

  • Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51:199–214

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA (2001) Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 25:455–467

    Article  CAS  PubMed  Google Scholar 

  • Langsjo JW, Kaisti KK, Aalto S, Hinkka S, Aantaa R, Oikonen V, Sipila H, Kurki T, Silvanto M, Scheinin H (2003) Effects of subanesthetic doses of ketamine on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology 99:614–623

    Article  PubMed  Google Scholar 

  • Langsjo JW, Salmi E, Kaisti KK, Aalto S, Hinkka S, Aantaa R, Oikonen V, Viljanen T, Kurki T, Silvanto M, Scheinin H (2004) Effects of subanesthetic ketamine on regional cerebral glucose metabolism in humans. Anesthesiology 100:1065–1071

    Article  PubMed  Google Scholar 

  • Leslie RA, James MF (2000) Pharmacological magnetic resonance imaging: a new application for functional MRI. Trends Pharmacol Sci 21:314–318

    Article  CAS  PubMed  Google Scholar 

  • Littlewood CL, Jones N, O’Neill MJ, Mitchell SN, Tricklebank M, Williams SCR (2005) Mapping the central effects of ketamine in the rat using pharmacological MRI. Institute of Psychiatry, King’s College London

  • Liu ZM, Schmidt KF, Sicard KM, Duong TQ (2004) Imaging oxygen consumption in forepaw somatosensory stimulation in rats under isoflurane anesthesia. Magn Reson Med 52:277–285

    Article  PubMed  Google Scholar 

  • Lodge D, Johnson KM (1990) Noncompetitive excitatory amino acid receptor antagonists. Trends Pharmacol Sci 11:81–86

    Article  CAS  PubMed  Google Scholar 

  • Lorrain DS, Baccei CS, Bristow LJ, Anderson JJ, Varney MA (2003) Effects of ketamine and n-methyl-d-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117:697–706

    Article  CAS  PubMed  Google Scholar 

  • MacDonald JF, Miljkovic Z, Pennefather P (1987) Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine. J Neurophysiol 58:251–266

    CAS  PubMed  Google Scholar 

  • Maclver MB, Mikulec AA, Amagasu SM, Monroe FA (1996) Volatile anesthetics depress glutamate transmission via presynaptic actions. Anesthesiology 85:823–834

    Article  CAS  PubMed  Google Scholar 

  • Malhotra AK, Adler CM, Kennison SD, Elman I, Pickar D, Breier A (1997) Clozapine blunts N-methyl-d-aspartate antagonist-induced psychosis: a study with ketamine. Biol Psychiatry 42:664–668

    Article  CAS  PubMed  Google Scholar 

  • Mayberg TS, Lam AM, Matta BF, Domino KB, Winn HR (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

    Article  CAS  PubMed  Google Scholar 

  • Mitchell SN, Greenslade RG, Cooper J (2001) LY393558, a 5-hydroxytryptamine reuptake inhibitor and 5-HT(1B/1D) receptor antagonist: effects on extracellular levels of 5-hydroxytryptamine in the guinea pig and rat. Eur J Pharmacol 432:19–27

    Article  CAS  PubMed  Google Scholar 

  • Moghaddam B, Adams B, Verma A, Daly D (1997) 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. J Neurosci 17:2921–2927

    CAS  PubMed  Google Scholar 

  • Morgan CJ, Mofeez A, Brandner B, Bromley L, Curran HV (2004) Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers. Neuropsychopharmacology 29:208–218

    Article  CAS  PubMed  Google Scholar 

  • Nagase K, Iida H, Dohi S (2003) Effects of ketamine on isoflurane- and sevoflurane-induced cerebral vasodilation in rabbits. J Neurosurg Anesthesiol 15:98–103

    Article  PubMed  Google Scholar 

  • Nakao S, Adachi T, Murakawa M, Shinomura T, Kurata J, Shichino T, Shibata M, Tocyama I, Kimura H, Mori K (1996) Halothane and diazepam inhibit ketamine-induced c-fos expression in the rat cingulate cortex. Anesthesiology 85:874–882

    Article  CAS  PubMed  Google Scholar 

  • Nakao S, Miyamoto E, Masuzawa M, Kambara T, Shingu K (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  CAS  PubMed  Google Scholar 

  • Newcomer JW, Farber NB, Jevtovic-Todorovic V, Selke G, Melson AK, Hershey T, Craft S, Olney JW (1999) Ketamine-induced NMDA receptor hypofunction as a model of memory impairment and psychosis. Neuropsychopharmacology 20:106–118

    Article  CAS  PubMed  Google Scholar 

  • Nishizawa N, Nakao S, Nagata A, Hirose T, Masuzawa M, Shingu K (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  CAS  PubMed  Google Scholar 

  • Ogawa S, Tank DW, Menon R, Ellermann JM, Kim SG, Merkle H, Ugurbil K (1992) Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci U S A 89:5951–5955

    Article  CAS  PubMed  Google Scholar 

  • Ohata H, Iida H, Nagase K, Dohi S (2001) The effects of topical and intravenous ketamine on cerebral arterioles in dogs receiving pentobarbital or isoflurane anesthesia. Anesth Analg 93:697–702

    Article  CAS  PubMed  Google Scholar 

  • Olney JW, Labruyere J, Price MT (1989) Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 244:1360–1362

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic

  • Pearce RA, Stringer JL, Lothman EW (1989) Effect of volatile anesthetics on synaptic transmission in the rat hippocampus. Anesthesiology 71:591–598

    Article  CAS  PubMed  Google Scholar 

  • Preece M, Mukherjee B, Huang CL, Hall LD, Leslie RA, James MF (2001) Detection of pharmacologically mediated changes in cerebral activity by functional magnetic resonance imaging: the effects of sulpiride in the brain of the anaesthetised rat. Brain Res 916:107–114

    Article  CAS  PubMed  Google Scholar 

  • Roberts TJ (2004) Structural and functional imaging in an experimental model of Huntingtons disease—mapping pathogenesis and potential therapy. Ph.D. thesis, University of London

  • Sakai K, Cho S, Fukusaki M, Shibata O, Sumikawa K (2000) The effects of propofol with and without ketamine on human cerebral blood flow velocity and CO(2) response. Anesth Analg 90:377–382

    Article  CAS  PubMed  Google Scholar 

  • Salmeron BJ, Stein EA (2002) Pharmacological applications of magnetic resonance imaging. Psychopharmacol Bull 36:102–129

    PubMed  Google Scholar 

  • Schwarz AJ, Zocchi A, Reese T, Gozzi A, Garzotti M, Varnier G, Curcuruto O, Sartori I, Girlanda E, Biscaro B, Crestan V, Bertani S, Heidbreder C, Bifone A (2004) Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration. Neuroimage 23:296–304

    Article  CAS  PubMed  Google Scholar 

  • Seeman P, Ko F, Tallerico T (2005) Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics. Mol Psychiatry 10(9):877–883

    Article  CAS  PubMed  Google Scholar 

  • Sharp FR, Tomitaka M, Bernaudin M, Tomitaka S (2001) Psychosis: pathological activation of limbic thalamocortical circuits by psychomimetics and schizophrenia? Trends Neurosci 24:330–334

    Article  CAS  PubMed  Google Scholar 

  • Sicard KM, Duong TQ (2005) Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals. Neuroimage 25:850–858

    Article  PubMed  Google Scholar 

  • Sicard K, Shen Q, Brevard ME, Sullivan R, Ferris CF, King JA, Duong TQ (2003) Regional cerebral blood flow and BOLD responses in conscious and anesthetized rats under basal and hypercapnic conditions: implications for functional MRI studies. J Cereb Blood Flow Metab 23:472–481

    Article  CAS  PubMed  Google Scholar 

  • Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17:143–155

    Article  PubMed  Google Scholar 

  • Smith AJ, Pekoe GM, Monroe PJ, Martin LL, Cabral MEY, Crisp T (1990) Ketamine analgesia in rats may be mediated by an interaction with opiate receptors. In: Domino EF (ed) Status of ketamine in anesthesiology. Ann Arbor, pp 199–209

  • Smith AT, Williams AL, Singh KD (2004) Negative BOLD in the visual cortex: evidence against blood stealing. Hum Brain Mapp 21:213–220

    Article  PubMed  Google Scholar 

  • Steward CA, Prior MJW, Chapman V, Morris PG, Marsden CA (2004) Mapping functional changes in rat brain in response to altered serotonergic function using BOLD fMRI. Proceedings (12th) of the International Society of Magnetic Resonance in Medicine, pp 1169

  • Svensson TH (2000) Dysfunctional brain dopamine systems induced by psychotomimetic NMDA-receptor antagonists and the effects of antipsychotic drugs. Brain Res Brain Res Rev 31:320–329

    Article  CAS  PubMed  Google Scholar 

  • Thomas CG, Harshman RA, Menon RS (2002) Noise reduction in BOLD-based fMRI using component analysis. Neuroimage 17:1521–1537

    Article  PubMed  Google Scholar 

  • Wong BS, Martin CD (1993) Ketamine inhibition of cytoplasmic calcium signalling in rat pheochromocytoma (PC-12) cells. Life Sci 53:PL359–PL364

    Article  CAS  PubMed  Google Scholar 

  • Worsley KJ, Friston KJ (1995) Analysis of fMRI time-series revisited—again. Neuroimage 2:173–181

    Article  CAS  PubMed  Google Scholar 

  • Xu H, Li SJ, Bodurka J, Zhao X, Xi ZX, Stein EA (2000) Heroin-induced neuronal activation in rat brain assessed by functional MRI. Neuroreport 11:1085–1092

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was funded by a BBSRC CASE studentship in collaboration with Eli Lilly. The MR imaging spectrometer was provided by the University of London Intercollegiate Research Service scheme and is located at Queen Mary College London and managed by Dr. Alasdair Preston. Jane Cooper provided technical assistance with all microdialysis experimentation. All experimentations comply with current UK legislation.

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Correspondence to Clare L. Littlewood.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-006-0544-7

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Littlewood, C.L., Jones, N., O’Neill, M.J. et al. Mapping the central effects of ketamine in the rat using pharmacological MRI. Psychopharmacology 186, 64–81 (2006). https://doi.org/10.1007/s00213-006-0344-0

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