Skip to main content
Log in

Methodological considerations in rat brain BOLD contrast pharmacological MRI

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale and objectives

Blood oxygen level dependent (BOLD) contrast pharmacological magnetic resonance imaging (phMRI) is an increasingly popular technique that allows the non-invasive investigation of spatial and temporal changes in rat brain function in response to pharmacological stimulation in vivo. Rat brain BOLD contrast phMRI is, at present, established in few neuropharmacological laboratories, and various issues associated with the technique require attention. The present review is primarily aimed at psychopharmacologists with no previous experience of phMRI, who are interested in the practical aspects that phMRI studies entail.

Results and discussion

Experimental and analytical considerations, including anaesthesia, physiological monitoring, drug dose and delivery, scanning protocols, statistical approaches and the interpretation of phMRI data, are discussed.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2 cg
Fig. 3

Similar content being viewed by others

References

  • Abo M, Suzuki M, Senoo A, Miyano S, Yamauchi H, Yonemoto K, Watanabe S, Edström L (2004) Influence of isoflurane concentration and hypoxia on functional magnetic resonance imaging for the detection of bicuculline-induced neuronal activation. Neurosignals 13:144–149

    Article  PubMed  CAS  Google Scholar 

  • Adachi YU, Watanabe K, Satoh T, Vizi ES (2001) Halothane potentiates the effect of methamphetamine and nomifensine on extracellular dopamine levels in rat striatum: a microdialysis study. Br J Anaesth 86:837–845

    Article  PubMed  CAS  Google Scholar 

  • Adachi YU, Aramaki Y, Satomoto M, Higuchi H, Watanabe K (2003) Halothane attenuated haloperidol and enhanced clozapine-induced dopamine release in the rat striatum. Neurochem Int 43:113–119

    Article  PubMed  CAS  Google Scholar 

  • Akgören N, Fabricius M, Lauritzen M (1994) Importance of nitric oxide for local increases of blood flow in rat cerebellar cortex during electrical stimulation. Proc Natl Acad Sci U S A 91:5903–5907

    PubMed  Google Scholar 

  • Anderson IM, Clark L, Elliott R, Kulkarni B, Williams SR, Deakin JFW (2002) 5-HT2C receptor activation by m-chlorophenylpiperazine detected in humans with fMRI. NeuroReport 13:1547–1551

    Article  PubMed  CAS  Google Scholar 

  • Angel A (1993) Central neuronal pathways and the process of anaesthesia. Br J Anaesth 71:148–163

    PubMed  CAS  Google Scholar 

  • Anzawa N, Kushikata T, Ohkawa H, Yoshida H, Kubota T, Matsuki A (2001) Increased noradrenaline release from rat preoptic area during and after sevoflurane and isoflurane anesthesia. Can J Anaesth 48:462–465

    PubMed  CAS  Google Scholar 

  • Arthurs OJ, Boniface S (2002) How well do we understand the neural origins of the fMRI BOLD signal? Trends Neurosci 25:27–31

    Article  PubMed  CAS  Google Scholar 

  • Austin VC, Blamire AM, Allers KA, Sharp T, Styles P, Matthews PM, Sibson NR (2005) Confounding effects of anesthesia on functional activation in rodent brain: a study of halothane and alpha-chloralose anesthesia. NeuroImage 24:92–100

    Article  PubMed  CAS  Google Scholar 

  • Bertorelli R, Hallström A, Hurd YL, Karlsson A, Consolo S, Ungerstedt U (1990) Anaesthesia effects on in vivo acetylcholine transmission; comparisons of radioenzymatic and HPLC assays. Eur J Pharmacol 175:79–83

    Article  PubMed  CAS  Google Scholar 

  • Bloom AS, Hoffmann RG, Fuller SA, Pankiewicz J, Harsch HH, Stein EA (1999) Determination of drug-induced changes in functional MRI signal using a pharmacokinetic model. Hum Brain Mapp 8:235–244

    Article  PubMed  CAS  Google Scholar 

  • Bonvento G, Charbonné R, Corrèze JL, Borredon J, Seylaz J, Lacombe P (1994) Is alpha-chloralose plus halothane induction a suitable anesthetic regimen for cerebrovascular research? Brain Res 665:213–221

    Article  PubMed  CAS  Google Scholar 

  • Bonvento G, Sibson N, Pellerin L (2002) Does glutamate image your thoughts? Trends Neurosci 25:359–364

    Article  PubMed  CAS  Google Scholar 

  • Borras MC, Becerra L, Ploghaus A, Gostic JM, DaSilva A, Gonzalez RG, Borsook D (2004) FMRI measurement of CNS responses to naloxone infusion and subsequent mild noxious thermal stimuli in healthy volunteers. J Neurophysiol 91:2723–2733

    Article  PubMed  CAS  Google Scholar 

  • Breiter HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD, Goodman JM, Kantor HL, Gastfriend DR, Riorden JP, Mathew RT, Rosen BR, Hyman SE (1997) Acute effects of cocaine on human brain activity and emotion. Neuron 19:591–611

    Article  PubMed  CAS  Google Scholar 

  • Brinker G, Bock C, Busch E, Krep H, Hossmann KA, Hoehn-Berlage M (1999) Simultaneous recording of evoked potentials and T2*-weighted MR images during somatosensory stimulation of rat. Magn Reson Med 41:469–473

    Article  PubMed  CAS  Google Scholar 

  • Broderick PA (1992) Distinguishing effects of cocaine i.v. and SC on mesoaccumbens dopamine and serotonin release with chloral hydrate anesthesia. Pharmacol Biochem Behav 43:929–937

    Article  PubMed  CAS  Google Scholar 

  • Brown RH, Walters DM, Greenberg RS, Mitzner W (1999) A method of endotracheal intubation and pulmonary functional assessment for repeated studies in mice. J Appl Physiol 87:2362–2365

    PubMed  CAS  Google Scholar 

  • Bui JD, Inglis BA, Nammari DR, Silver XS, Mercer E, Tofollo S, Phillips MI, Mareci TH (1997) FMRI visualization of neuronal activation following direct neurochemical stimulation of the brain: a novel approach to brain mapping. Proc 5th Int Soc Magn Reson Med 730

    Google Scholar 

  • Burke M, Schwindt W, Ludwig U, Hennig J, Hoehn M (2000) Facilitation of electric forepaw stimulation-induced somatosensory activation in rats by additional acoustic stimulation: an fMRI investigation. Magn Reson Med 44:317–321

    Article  PubMed  CAS  Google Scholar 

  • Carlsson C, Hägerdal M, Siesjö BK (1975) Increase in cerebral oxygen uptake and blood flow in immobilization stress. Acta Physiol Scand 95:206–208

    PubMed  CAS  Google Scholar 

  • Carlsson C, Hägerdal M, Siesjö BK (1976) The effect of hyperthermia upon oxygen consumption and upon organic phosphates, glycolytic metabolites, citric and cycle intermediates and associated amino acids in rat cerebral cortex. J Neurochem 26:1001–1006

    PubMed  CAS  Google Scholar 

  • Cash D, Lowe AS, Roberts TJ, Ireland MD, Williams SCR (2002) In vivo mapping of mouse brain response to d-amphetamine using bold contrast FMRI. J Psychopharmacol 16:OM3

    Google Scholar 

  • Cash D, Read SJ, Lythgoe DJ, Williams SCR, Roberts TJ, Ireland MD, Smart SC, Hunter AJ (2003) Autoradiographic and functional MRI of rat brain response to amphetamine under halothane and alpha-chloralose anaesthesia. J Psychopharmacol 17:A37

    Google Scholar 

  • Chen YCI, Galpern WR, Brownell AL, Matthews RT, Bogdanov M, Isacson O, Keltner JR, Beal MF, Rosen BR, Jenkins BG (1997) Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: correlation with PET, microdialysis, and behavioral data. Magn Reson Med 38:389–398

    PubMed  CAS  Google Scholar 

  • Chen YCI, Brownell AL, Galpern W, Isacson O, Bogdanov M, Beal MF, Livni E, Rosen BR, Jenkins BG (1999) Detection of dopaminergic cell loss and neural transplantation using pharmacological MRI, PET and behavioral assessment. NeuroReport 10:2881–2886

    PubMed  CAS  Google Scholar 

  • Chen YCI, Mandeville JB, Nguyen TV, Talele A, Cavagna F, Jenkins BG (2001) Improved mapping of pharmacologically induced neuronal activation using the IRON technique with superparamagnetic blood pool agents. J Magn Reson Imaging 14:517–524

    Article  PubMed  CAS  Google Scholar 

  • Chen Z, Silva AC, Yang J, Shen J (2005) Elevated endogenous GABA level correlates with decreased fMRI signals in the rat brain during acute inhibition of GABA transaminase. J Neurosci Res 79:383–391

    Article  PubMed  CAS  Google Scholar 

  • Dam M, Ori C, Pizzolato G, Ricchieri GL, Pellegrini A, Giron GP, Battistin L (1990) The effects of propofol anesthesia on local cerebral glucose utilization in the rat. Anesthesiology 73:499–505

    PubMed  CAS  Google Scholar 

  • Detsch O, Vahle-Hinz C, Kochs E, Siemers M, Bromm B (1999) Isoflurane induces dose-dependent changes of thalamic somatosensory information transfer. Brain Res 829:77–89

    Article  PubMed  CAS  Google Scholar 

  • Devlin JT, Russell RP, Davis MH, Price CJ, Wilson J, Moss HE, Matthews PM, Tyler LK (2000) Susceptibility-induced loss of signal: comparing PET and fMRI on a semantic task. NeuroImage 11:589–600

    Article  PubMed  CAS  Google Scholar 

  • Di Salle F, Esposito F, Elefante A, Scarabino T, Volpicelli A, Cirillo S, Elefante R, Seifritz E (2003) High field functional MRI. Eur J Radiol 48:138–145

    Article  PubMed  Google Scholar 

  • Dixon AL, Shah YB, Prior MJW, Morris PG, Young AMJ (2003) Functional magnetic resonance imaging of dopamine systems in the rat. Proc 10th Int Conf In Vivo Methods, pp 281–283

  • Dixon AL, Cash D, Williams SCR, Finnerty GT (2004) Correspondence of fMRI and 2-deoxyglucose representations of the rodent forepaw in primary somatosensory cortex under different anaesthetics. Proc 12th Int Soc Magn Reson Med 1118

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

    Article  PubMed  CAS  Google Scholar 

  • Dringenberg HC, Vanderwolf CH (1995) Some general anesthetics reduce serotonergic neocortical activation and enhance the action of serotonergic antagonists. Brain Res Bull 36:285–292

    Article  PubMed  CAS  Google Scholar 

  • Dudley RE, Nelson SR, Samson F (1982) Influence of chloralose on brain regional glucose utilization. Brain Res 233:173–180

    Article  PubMed  CAS  Google Scholar 

  • Duong TQ, Yacoub E, Adriany G, Hu XP, Ugurbil K, Kim SG (2003) Microvascular BOLD contribution at 4 and 7 T in the human brain: gradient-echo and spin-echo fMRI with suppression of blood effects. Magn Reson Med 49:1019–1027

    Article  PubMed  Google Scholar 

  • Eugène F, Lévesque J, Mensour B, Leroux JM, Beaudoin G, Bourgouin P,Beauregard M (2003) The impact of individual differences on the neural circuitry underlying sadness. NeuroImage 19:354–364

    Article  PubMed  Google Scholar 

  • Febo M, Segarra AC, Tenney JR, Brevard ME, Duong TQ, Ferris CF (2004) Imaging cocaine-induced changes in the mesocorticolimbic dopaminergic system of conscious rats. J Neurosci Methods 139:167–176

    Article  PubMed  CAS  Google Scholar 

  • Febo M, Segarra AC, Nair G, Schmidt K, Duong TQ, Ferris CF (2005) The neural consequences of repeated cocaine exposure revealed by functional MRI in awake rats. Neuropsychopharmacology (in press)

  • Finck AD, Ngai SH, Berkowitz BA (1977) Antagonism of general anesthesia by naloxone in the rat. Anesthesiology 46:241–245

    PubMed  CAS  Google Scholar 

  • Fink-Jensen A, Ingwersen SH, Nielsen PG, Hansen L, Nielsen EB, Hansen AJ (1994) Halothane anesthesia enhances the effect of dopamine uptake inhibition on interstitial levels of striatal dopamine. Naunyn-Schmiedeberg’s Arch Pharmacol 350:239–244

    PubMed  CAS  Google Scholar 

  • Flecknell PA (1987) Laboratory animal anaesthesia. Academic Press, London

    Google Scholar 

  • Ford AP, Marsden CA (1986) Influence of anaesthetics on rat striatal dopamine metabolism in vivo. Brain Res 379:162–166

    Article  PubMed  CAS  Google Scholar 

  • Frankenstein U, Wennerberg A, Richter W, Bernstein C, Morden D, Rémy F, McIntyre M (2003) Activation and deactivation in blood oxygenation level dependent functional magnetic resonance imaging. Concepts Magn Reson 16A:63–70

    Article  CAS  Google Scholar 

  • Franks NP, Lieb WR (1998) Which molecular targets are most relevant to general anaesthesia? Toxicol Lett 100–101:1–8

    Article  PubMed  Google Scholar 

  • Fricke ST, Vink R, Chiodo C, Cernak I, Ileva L, Faden AI (2004) Consistent and reproducible slice selection in rodent brain using a novel stereotaxic device for MRI. J Neurosci Methods 136:99–102

    Article  PubMed  CAS  Google Scholar 

  • Frietsch T, Krafft P, Piepgras A, Lenz C, Kuschinsky W, Waschke KF (2000) Relationship between local cerebral blood flow and metabolism during mild and moderate hypothermia in rats. Anesthesiology 92:754–763

    Article  PubMed  CAS  Google Scholar 

  • Friman O, Borga M, Lundberg P, Knutsson H (2004) Detection and detrending in fMRI data analysis. NeuroImage 22:645–655

    Article  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 

  • Friston KJ, Holmes AP, Worsley KJ (1999) How many subjects constitute a study? NeuroImage 10:1–5

    Article  PubMed  CAS  Google Scholar 

  • Glen JB (1980) Animal studies of the anaesthetic activity of ICI 35 868. Br J Anaesth 52:731–742

    PubMed  CAS  Google Scholar 

  • Golay X, De Zwart JA, Ho Y-CL, Sitoh Y-Y (2004) Parallel imaging techniques in functional MRI. Top Magn Reson Imaging 15:255–265

    Article  PubMed  Google Scholar 

  • Gozzi A, Schwarz AJ, Reese T, Crestan V, Bertani S, Turrini G, Corsi M, Bifone A (2005) Functional magnetic resonance mapping of intracerebroventricular infusion of a neuroactive peptide in the anaesthetised rat. J Neurosci Methods 142:115–124

    Article  PubMed  CAS  Google Scholar 

  • Griffiths R, Norman RI (1993) Effects of anaesthetics on uptake, synthesis and release of transmitters. Br J Anaesth 71:96–107

    PubMed  CAS  Google Scholar 

  • Grome JJ, McCulloch J (1983) The effects of apomorphine upon local cerebral glucose utilization in conscious rats and in rats anesthetized with chloral hydrate. J Neurochem 40:569–576

    PubMed  CAS  Google Scholar 

  • Hagino H, Tabuchi E, Kurachi M, Saitoh O, Sun YJ, Kondoh T, Ono T, Torii K (1998) Effects of D-2 dopamine receptor agonist and antagonist on brain activity in the rat assessed by functional magnetic resonance imaging. Brain Res 813:367–373

    Article  PubMed  CAS  Google Scholar 

  • Hajnal JV, Myers R, Oatridge A, Schwieso JE, Young IR, Bydder GM (1994) Artifacts due to stimulus correlated motion in functional imaging of the brain. Magn Reson Med 31:283–291

    PubMed  CAS  Google Scholar 

  • Hamilton ME, Mele A, Pert A (1992) Striatal extracellular dopamine in conscious vs. anesthetized rats: effects of chloral hydrate anesthetic on responses to drugs of different classes. Brain Res 597:1–7

    Article  PubMed  CAS  Google Scholar 

  • Hansen TD, Warner DS, Todd MM, Vust LJ, Trawick DC (1988) Distribution of cerebral blood flow during halothane versus isoflurane anesthesia in rats. Anesthesiology 69:332–337

    PubMed  CAS  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 

  • Hedenqvist P, Hellebrekers LJ (2003) Laboratory animal analgesia, anesthesia, and euthanasia. In: Hau J, Van Hoosier GL Jr (eds) Handbook of laboratory animal science, vol. 1: essential principles and practices. CRC Press, Florida, pp 413–455

    Google Scholar 

  • Hedlund LW, Cofer GP, Owen SJ, Allan JG (2000) MR-compatible ventilator for small animals: computer-controlled ventilation for proton and noble gas imaging. Magn Reson Imaging 18:753–759

    Article  PubMed  CAS  Google Scholar 

  • Heeger DJ, Boynton GM, Demb JB, Seidemann E, Newsome WT (1999) Motion opponency in visual cortex. J Neurosci 19:7162–7174

    PubMed  CAS  Google Scholar 

  • Heimburger M, Pages N, Davy M, el Rawadi C, Cohen Y, Bohuon C (1992) Effects of chloral, chloralose and pentobarbitone on monoamine and (neuropeptide Y) NPY levels in various tissues in the rat. Res Commun Chem Pathol Pharmacol 76:183–191

    PubMed  CAS  Google Scholar 

  • Herkenham M (1987) Mismatches between neurotransmitter and receptor localizations in brain: observations and implications. Neuroscience 23:1–38

    Article  PubMed  CAS  Google Scholar 

  • Honey GD, Bullmore ET, Soni W, Varatheesan M, Williams SCR, Sharma T (1999) Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Natl Acad Sci U S A 96:13432–13437

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Jueptner M, Weiller C (1995) Review—does measurement of regional cerebral blood-flow reflect synaptic activity? Implications for PET and fMRI. NeuroImage 2:148–156

    Article  PubMed  CAS  Google Scholar 

  • Kalén P, Kokaia M, Lindvall O, Björklund A (1988) Basic characteristics of noradrenaline release in the hippocampus of intact and 6-hydroxydopamine-lesioned rats as studied by in vivo microdialysis. Brain Res 474:374–379

    Article  PubMed  Google Scholar 

  • Kalisch R, Elbel GK, Gössl 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  PubMed  CAS  Google Scholar 

  • Kalisch R, Salomé N, Platzer S, Wigger A, Czisch M, Sommer W, Singewald N, Heilig M, Berthele A, Holsboer F, Landgraf R, Auer DP (2004) High trait anxiety and hyporeactivity to stress of the dorsomedial prefrontal cortex: a combined phMRI and Fos study in rats. NeuroImage 23:382–391

    Article  PubMed  Google Scholar 

  • Kalisch R, Delfino M, Murer MG, Auer DP (2005) The phenylephrine blood pressure clamp in pharmacologic MRI: reduction of systemic confounds and improved detectability of drug-induced BOLD signal changes. Psychopharmacology, this issue

    Google Scholar 

  • Kannurpatti SS, Biswal BB (2004) Effect of anesthesia on CBF, MAP and fMRI-BOLD signal in response to apnea. Brain Res 1011:141–147

    Article  PubMed  CAS  Google Scholar 

  • Keilholz SD, Silva AC, Raman M, Merkle H, Koretsky AP (2004) Functional MRI of the rodent somatosensory pathway using multislice echo planar imaging. Magn Reson Med 52:89–99

    Article  PubMed  Google Scholar 

  • Khubchandani M, Jagannathan NR (2004) Simultaneous electrophysiology and functional magnetic resonance imaging studies in conscious rats. Methods Enzymol 385:63–84

    PubMed  CAS  Google Scholar 

  • Kim S-G, Ugurbil K (2003) High-resolution functional magnetic resonance imaging of the animal brain. Methods 30:28–41

    Article  PubMed  CAS  Google Scholar 

  • Kreuter JD, Mattson BJ, Wang B, You ZB, Hope BT (2004) Cocaine-induced fos expression in rat striatum is blocked by chloral hydrate or urethane. Neuroscience 127:233–242

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kuriwaki J, Nishijo H, Kondoh T, Uwano T, Torii K, Katsuki M, Ono T (2004) Comparison of brain activity between dopamine D2 receptor-knockout and wild mice in response to dopamine agonist and antagonist assessed by fMRI. Neurosignals 13:227–240

    Article  PubMed  CAS  Google Scholar 

  • Lahti KM, Ferris CF, Li FH, Sotak CH, King JA (1999) Comparison of evoked cortical activity in conscious and propofol-anesthetized rats using functional MRI. Magn Reson Med 41:412–416

    Article  PubMed  CAS  Google Scholar 

  • Lauritzen M, Gold L (2003) Brain function and neurophysiological correlates of signals used in functional neuroimaging. J Neurosci 23:3972–3980

    PubMed  CAS  Google Scholar 

  • Lee SP, Silva AC, Ugurbil K, Kim SG (1999) Diffusion-weighted spin-echo fMRI at 9.4 T: microvascular/tissue contribution to BOLD signal changes. Magn Reson Med 42:919–928

    Article  PubMed  CAS  Google Scholar 

  • Lindauer U, Villringer A, Dirnagl U (1993) Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics. Am J Physiol 264:H1223–H1228

    PubMed  CAS  Google Scholar 

  • Littlewood CL, Jones N, Mitchell SN, Tricklebank MD, O’Neill MJ, Williams SCR (2004) Measurement of the functional actions of ketamine in the rat brain using locomotor activity, microdialysis and phMRI imaging techniques. Proc 12th Int Soc Magn Reson Med 643

  • Lowe MJ, Russell DP (1999) Treatment of baseline drifts in fMRI time series analysis. J Comput Assist Tomogr 23:463–473

    Article  PubMed  CAS  Google Scholar 

  • Lowe AS, Williams SCR, Symms MR, Stolerman IP, Shoaib M (2002) Functional magnetic resonance neuroimaging of drug dependence: naloxone-precipitated morphine withdrawal. NeuroImage 17:902–910

    Article  PubMed  Google Scholar 

  • Ludwig R, Bodgdanov G, King J, Allard A, Ferris CF (2004) A dual resonator system for high-field functional magnetic resonance imaging of small animals. J Neurosci Methods 132:125–135

    Article  PubMed  CAS  Google Scholar 

  • Luo F, Wu G, Li Z, Li SJ (2003) Characterization of effects of mean arterial blood pressure induced by cocaine and cocaine methiodide on BOLD signals in rat brain. Magn Reson Med 49:264–270

    Article  PubMed  Google Scholar 

  • Luo F, Xi ZX, Wu GH, Liu C, Gardner EL, Li SJ (2004) Attenuation of brain response to heroin correlates with the reinstatement of heroin-seeking in rats by fMRI. NeuroImage 22:1328–1335

    Article  PubMed  Google Scholar 

  • Malisza KL, Docherty JC (2001) Capsaicin as a source for painful stimulation in functional MRI. J Magn Reson Imaging 14:341–347

    Article  PubMed  CAS  Google Scholar 

  • Mandeville JB, Jenkins BG, Kosofsky BE, Moskowitz MA, Rosen BR, Marota JJ (2001) Regional sensitivity and coupling of BOLD and CBV changes during stimulation of rat brain. Magn Reson Med 45:443–447

    Article  PubMed  CAS  Google Scholar 

  • Marota JJ, Mandeville JB, Weisskoff RM, Moskowitz MA, Rosen BR, Kosofsky BE (2000) Cocaine activation discriminates dopaminergic projections by temporal response: an fMRI study in rat. NeuroImage 11:13–23

    Article  PubMed  CAS  Google Scholar 

  • Massott M, Longo VG (1978) Alpha-chloralose and the central dopaminergic system. J Pharm Pharmacol 30:667

    PubMed  CAS  Google Scholar 

  • Matsuoka H, Watanabe Y, Isshiki A, Quock RM (1999) Increased production of nitric oxide metabolites in the hippocampus under isoflurane anaesthesia in rats. Eur J Anaesthesiol 16:216–224

    Article  PubMed  CAS  Google Scholar 

  • Mayer P, Erdtmann-Vourliotis M, Riechert U, Ammon S, Höllt V (2002) Mild stress sensitizes the brain’s response to morphine. Brain Res Mol Brain Res 104:143–147

    Article  PubMed  CAS  Google Scholar 

  • McCulloch J, Savaki HE, Jehle J, Sokoloff L (1982) Local cerebral glucose utilization in hypothermic and hyperthermic rats. J Neurochem 39:255–258

    PubMed  CAS  Google Scholar 

  • McKeown MJ, Hansen LK, Sejnowsk TJ (2003) Independent component analysis of functional MRI: what is signal and what is noise? Curr Opin Neurobiol 13:620–629

    Article  PubMed  CAS  Google Scholar 

  • Mereu G, Fadda F, Gessa GL (1984) Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats. Brain Res 292:63–69

    Article  PubMed  CAS  Google Scholar 

  • Miller MJ, Chen NK, Li L, Tom B, Weiss C, Disterhoft JF, Wyrwicz AM (2003) fMRI of the conscious rabbit during unilateral classical eyeblink conditioning reveals bilateral cerebellar activation. J Neurosci 23:11753–11758

    PubMed  CAS  Google Scholar 

  • Müller-Gärtner HW (1998) Imaging techniques in the analysis of brain function and behaviour. Trends Biotechnol 16:122–130

    Article  PubMed  Google Scholar 

  • Ngai SH, Cheney DL, Finck AD (1978) Acetylcholine concentrations and turnover in rat brain structures during anesthesia with halothane, enflurane, and ketamine. Anesthesiology 48:4–10

    PubMed  CAS  Google Scholar 

  • Nguyen TV, Brownell AL, Iris Chen YC, Livni E, Coyle JT, Rosen BR, Cavagna F, Jenkins BG (2000) Detection of the effects of dopamine receptor supersensitivity using pharmacological MRI and correlations with PET. Synapse 36:57–65

    Article  PubMed  CAS  Google Scholar 

  • Nieoullon A, Dusticier N (1980) Effects of alpha-chloralose on the activity of the nigrostriatal dopaminergic system in the cat. Eur J Pharmacol 65:403–410

    Article  PubMed  CAS  Google Scholar 

  • Norris DG (2003) High field human imaging. J Magn Reson Imaging 18:519–529

    Article  PubMed  Google Scholar 

  • Ogawa S, Lee TM, Kay AR, Tank DW (1990) Brain Magnetic Resonance Imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A 87:9868–9872

    PubMed  CAS  Google Scholar 

  • Opacka-Juffry J, Ahier RG, Cremer JE (1991) Nomifensine-induced increase in extracellular striatal dopamine is enhanced by isoflurane anaesthesia. Synapse 7:169–171

    Article  PubMed  CAS  Google Scholar 

  • Ori C, Dam M, Pizzolato G, Battistin L, Giron G (1986) Effects of isoflurane anesthesia on local cerebral glucose utilization in the rat. Anesthesiology 65:152–156

    PubMed  CAS  Google Scholar 

  • Pain L, Gobaille S, Schleef C, Aunis D, Oberling P (2002) In vivo dopamine measurements in the nucleus accumbens after nonanesthetic and anesthetic doses of propofol in rats. Anesth Analg 95:915–919

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1996) The rat brain in stereotaxic coordinates. Academic Press, California

    Google Scholar 

  • Peeters RR, Tindemans I, De Schutter E, Van der Linden A (2001) Comparing BOLD fMRI signal changes in the awake and anesthetized rat during electrical forepaw stimulation. Magn Reson Imaging 19:821–826

    Article  PubMed  CAS  Google Scholar 

  • Peschanski M, Villanueva L, Le Bars D, Bernard JF (1986) Differential metabolic activity in the brain during deep halothane anesthesia. A qualitative study using [3H]deoxyglucose. Neurosci Lett 71:1–6

    Article  PubMed  CAS  Google Scholar 

  • Pizzolato G, Soncrant TT, Rapoport SI (1984) Haloperidol and cerebral metabolism in the conscious rat: relation to pharmacokinetics. J Neurochem 43:724–732

    PubMed  CAS  Google Scholar 

  • Pocock G, Richards CD (1993) Excitatory and inhibitory synaptic mechanisms in anaesthesia. Br J Anaesth 71:134–147

    PubMed  CAS  Google Scholar 

  • Preece M, Mukherjee B, Huang CLH, 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  PubMed  CAS  Google Scholar 

  • Reese T, Bjelke B, Porszasz R, Baumann D, Bochelen D, Sauter A, Rudin M (2000) Regional brain activation by bicuculline visualized by functional magnetic resonance imaging. Time-resolved assessment of bicuculline-induced changes in local cerebral blood volume using an intravascular contrast agent. NMR Biomed 13:43–49

    Article  PubMed  CAS  Google Scholar 

  • Richards CD (1998) What the actions of anaesthetics on fast synaptic transmission reveal about the molecular mechanism of anaesthesia. Toxicol Lett 101:41–50

    Article  Google Scholar 

  • Sachdev RNS, Champney GC, Lee H, Price RR, Pickens DR, Morgan VL, Stefansic JD, Melzer P, Ebner FF (2003) Experimental model for functional magnetic resonance imaging of somatic sensory cortex in the unanesthetized rat. NeuroImage 19:742–750

    Article  PubMed  Google Scholar 

  • Scanley BE, Kennan RP, Gore JC (2001) Changes in rat cerebral blood volume due to modulation of the 5-HT(1A) receptor measured with susceptibility enhanced contrast MRI. Brain Res 913:149–155

    Article  PubMed  CAS  Google Scholar 

  • Schwarz A, Gozzi A, Reese T, Bertani S, Crestan V, Hagan J, Heidbreder C, Bifone A (2004a) Selective dopamine D-3 receptor antagonist SB-277011-A potentiates phMRI response to acute amphetamine challenge in the rat brain. Synapse 54:1–10

    Article  PubMed  CAS  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 (2004b) 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  PubMed  CAS  Google Scholar 

  • Schweinhardt P, Fransson P, Olson L, Spenger C, Andersson JLR (2003) A template for spatial normalisation of MR images of the rat brain. J Neurosci Methods 129:105–113

    Article  PubMed  Google Scholar 

  • Schwieler L, Delbro DS, Engberg G, Erhardt S (2003) The anaesthetic agent propofol interacts with GABA(B)-receptors: an electrophysiological study in rat. Life Sci 72:2793–2801

    Article  PubMed  CAS  Google Scholar 

  • Shah YB (2002) Applications of magnetic resonance imaging techniques in neuropharmacology. Ph.D. thesis. University of Nottingham

  • Shah YB, Prior MJW, Dixon AL, Morris PG, Marsden CA (2004) Detection of cannabinoid agonist evoked increase in BOLD contrast in rats using functional magnetic resonance imaging. Neuropharmacology 46:379–387

    Article  PubMed  CAS  Google Scholar 

  • Shah YB, Haynes L, Prior MJW, Marsden CA, Morris PG, Chapman V (2005) Functional magnetic resonance imaging studies of opioid receptor mediated modulation of noxious-evoked BOLD contrast in rats. Psychopharmacology, this issue

  • Shichino T, Murakawa M, Adachi T, Nakao S, Shinomura T, Kurata J, Mori K (1997) Effects of isoflurane on in vivo release of acetylcholine in the rat cerebral cortex and striatum. Acta Anaesthesiol Scand 41:1335–1340

    Article  PubMed  CAS  Google Scholar 

  • Shimokawa A, Jin QH, Ishizuka Y, Kunitake T, Takasaki M, Kannan H (1998) Effects of anesthetics on norepinephrine release in the hypothalamic paraventricular nucleus region of awake rats. Neurosci Lett 244:21–24

    Article  PubMed  CAS  Google Scholar 

  • Shoaib M, Lowe AS, Williams SCR (2004) Imaging localised dynamic changes in the nucleus accumbens following nicotine withdrawal in rats. NeuroImage 22:847–854

    Article  PubMed  Google Scholar 

  • Shyr MH, Tsai TH, Yang CH, Chen HM, Ng HF, Tan PP (1997) Propofol anesthesia increases dopamine and serotonin activities at the somatosensory cortex in rats: a microdialysis study. Anesth Analg 84:1344–1348

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Silva AC, Zhang WG, Williams DS, Koretsky AP (1995) Multislice MRI of rat brain perfusion during amphetamine stimulation using arterial spin labelling. Magn Reson Med 33:209–214

    PubMed  CAS  Google Scholar 

  • Smith AM, Lewis BK, Ruttimann UE, Ye FQ, Sinnwell TM, Yang Y, Duyn JH, Frank JA (1999) Investigation of low frequency drift in fMRI signal. NeuroImage 9:526–533

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (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

    PubMed  CAS  Google Scholar 

  • Ståhle L, Collin AK, Ungerstedt U (1990) Effects of halothane anaesthesia on extracellular levels of dopamine, dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindolacetic acid in rat striatum: a microdialysis study. Naunyn-Schmiedeberg’s Arch Pharmacol 342:136–140

    Article  PubMed  Google Scholar 

  • Stefanovic B, Warnking JM, Pike GB (2004) Hemodynamic and metabolic responses to neuronal inhibition. NeuroImage 22:771–778

    Article  PubMed  Google Scholar 

  • Stein EA, Pankiewicz J, Harsch HH, Cho JK, Fuller SA, Hoffmann RG, Hawkins M, Rao SM, Bandettini PA, Bloom AS (1998) Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. Am J Psychiatry 155:1009–1015

    PubMed  CAS  Google Scholar 

  • Steward CA, Prior MJW, Chapman V, Shah YB, Morris PG, Marsden CA (2003) Functional mapping in rat brain using BOLD contrast fMRI: methodological issues. Proc 10th Int Conf In Vivo Methods, pp 284–286

    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. Proc 12th Int Soc Magn Reson Med, pp 1169

  • Suria A, Rasheed F (1994) Evidence for involvement of amino acid neurotransmitters in anesthesia and naloxone induced reversal of respiratory paralysis. Life Sci 54:2021–2033

    Article  PubMed  CAS  Google Scholar 

  • Tabuchi E, Yokawa T, Mallick H, Inubushi T, Kondoh T, Ono T, Torii K (2002) Spatio-temporal dynamics of brain activated regions during drinking behavior in rats. Brain Res 951:270–279

    Article  PubMed  CAS  Google Scholar 

  • Tanabe J, Miller D, Tregellas J, Freedman R, Meyer FG (2002) Comparison of detrending methods for optimal fMRI preprocessing. NeuroImage 15:902–907

    Article  PubMed  Google Scholar 

  • Tao R, Auerbach SB (1994) Anesthetics block morphine-induced increases in serotonin release in rat CNS. Synapse 18:307–314

    Article  PubMed  CAS  Google Scholar 

  • Thomas DL, Lythgoe MF, Pell GS, Calamante F, Ordidge RJ (2000) The measurement of diffusion and perfusion in biological systems using magnetic resonance imaging. Phys Med Biol 45:R97–R138

    Article  PubMed  CAS  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 

  • Tuor UI, Edvinsson L, McCulloch J (1986) Catecholamines and the relationship between cerebral blood flow and glucose use. Am J Physiol 251:H824–H833

    PubMed  CAS  Google Scholar 

  • Tuor UI, Malisza K, Foniok T, Papadimitropoulos R, Jarmasz M, Somorjai R, Kozlowski P (2000) Functional magnetic resonance imaging in rats subjected to intense electrical and noxious chemical stimulation of the forepaw. Pain 87:315–324

    Article  PubMed  CAS  Google Scholar 

  • Tuor UI, McKenzie E, Tomanek B (2002) Functional magnetic resonance imaging of tonic pain and vasopressor effects in rats. Magn Reson Imaging 20:707–712

    Article  PubMed  CAS  Google Scholar 

  • Turner R, Howseman A, Rees GE, Josephs O, Friston K (1998) Functional magnetic resonance imaging of the human brain: data acquisition and analysis. Exp Brain Res 123:5–12

    Article  PubMed  CAS  Google Scholar 

  • Ueki M, Mies G, Hossmann KA (1992) Effect of alpha-chloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat. Acta Anaesthesiol Scand 36:318–322

    PubMed  CAS  Google Scholar 

  • Verberne AJM, Owens NC (1998) Cortical modulation of the cardiovascular system. Prog Neurobiol 54:149–168

    Article  PubMed  CAS  Google Scholar 

  • Völlm BA, de Araujo IE, Cowen PJ, Rolls ET, Kringelbach ML, Smith KA, Jezzard P, Heal RJ, Matthews PM (2004) Methamphetamine activates reward circuitry in drug naive human subjects. Neuropsychopharmacology 29:1715–1722

    Article  PubMed  CAS  Google Scholar 

  • Wade AR (2002) The negative BOLD signal unmasked. Neuron 36:993–995

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Kikuchi T, Sakai M, Wu JL, Sato K, Okumura F (2000) Age-related modifications of effects of ketamine and propofol on rat hippocampal acetylcholine release studied by in vivo brain microdialysis. Acta Anaesthesiol Scand 44:112–117

    Article  PubMed  CAS  Google Scholar 

  • Warenycia MW, McKenzie GM (1988) Excitation of striatal neurons by dexamphetamine is not abolished by either chloral hydrate or urethane anaesthesia. Neuropharmacology 27:1309–1312

    Article  PubMed  CAS  Google Scholar 

  • West MO (1998) Anesthetics eliminate somatosensory-evoked discharges of neurons in the somatotopically organized sensorimotor striatum of the rat. J Neurosci 18:9055–9068

    PubMed  CAS  Google Scholar 

  • Whitehead KJ, Rose S, Jenner P (2004) Halothane anesthesia affects NMDA-stimulated cholinergic and GABAergic modulation of striatal dopamine efflux and metabolism in the rat in vivo. Neurochem Res 29:835–842

    Article  PubMed  CAS  Google Scholar 

  • Xi ZX, Wu GH, Stein EA, Li SJ (2002) GABAergic mechanisms of heroin-induced brain activation assessed with functional MRI. Magn Reson Med 48:838–843

    Article  PubMed  CAS  Google Scholar 

  • Xi ZX, Wu GH, Stein EA, Li SJ (2004) Opiate tolerance by heroin self-administration: an MRI study in rat. Magn Reson Med 52:108–114

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Yamamoto T, Kida I (1996) Application of transcutaneous blood carbon dioxide monitoring to the magnetic resonance imaging of rat. J Med Eng Technol 20:164–168

    PubMed  CAS  Google Scholar 

  • Zhang Z, Andersen A, Grondin R, Barber T, Avison R, Gerhardt G, Gash D (2001) Pharmacological MRI mapping of age-associated changes in basal ganglia circuitry of awake rhesus monkeys. NeuroImage 14:1159–1167

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

C.A.S. was funded by the Medical Research Council and wishes to thank D.P. Auer for helpful discussions regarding the manuscript. All procedures at the University of Nottingham were performed with local ethical and UK Home Office approval.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. A. Steward.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steward, C.A., Marsden, C.A., Prior, M.J.W. et al. Methodological considerations in rat brain BOLD contrast pharmacological MRI. Psychopharmacology 180, 687–704 (2005). https://doi.org/10.1007/s00213-005-2213-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-2213-7

Keywords

Navigation