Functional Brain Imaging and Large Animal Research

  • Kathelijne Peremans
  • Kurt Audenaert
  • F. Verschooten
  • Andreas Otte
  • Guido Slegers
  • Rudi Dierckx


In this chapter a review will be given on brain functional imaging research on large animals in order to contribute to a better understanding of human neuropsychiatric disorders and explore treatment options. In general, smaller laboratory animals such as mice and rats have been extensively used. Nevertheless, the utilization of larger animals has definite advantages because of their larger brain size, omitting the need for dedicated equipment (micro-PET or -SPET). First, large animal models, usually primate models, are used to obtain information on the pharmacokinetics and pharmacodynamics of newly developed drugs and the dosage at which maximal response and least side effects occur. They are also used to investigate normal physiology and interaction of several neurotransmitter systems and the effects of substances of abuse on brain function and chemistry. Finally, models of animal behaviour, both in natural conditions or after artificially (chemically or surgically) induced lesions, are used to enlighten the biological base of several human brain disorders.


Receptor Occupancy Regional Cerebral Blood Flow Functional Brain Image Thromboembolic Stroke Cerebral Blood Flow Response 
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  1. Andree B, Halldin C, Thorberg SO, Sandell J, Farde L (2000) Use of PET and the radioligand [carbonyl-(11)C]WAY-100635 in psychotropic drug development. Nucl Med Biol 27:515–521PubMedCrossRefGoogle Scholar
  2. Asberg M, Traskman L, Thoren P (1976) 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry 33:1193–1197PubMedCrossRefGoogle Scholar
  3. Avery RA, Franowicz JS, Studholme C, van Dyck CH, Arnsten AF (2000) The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task. Neuropsychopharmacology 23:240–249PubMedCrossRefGoogle Scholar
  4. Biver F, Lotstra F, Monclus M, Wikler D, Damhaut P, Mendelwicz J, Goldman S (1996) Sex difference in 5-HT2 receptor in the living human brain. Neurosci Lett 204:25–28PubMedCrossRefGoogle Scholar
  5. Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, Eckelman WC, Pickar D (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A 94:2569–2574CrossRefGoogle Scholar
  6. Brody BA, Pribram KH (1978) The role of frontal and parietal cortex in cognitive processing: tests of spatial and sequence functions. Brain 101:607–633PubMedCrossRefGoogle Scholar
  7. Brody E, Rosvold H (1952) Influence of prefrontal lobotomy on social interaction in a monkey group. Psychosom Med 14:406–415PubMedGoogle Scholar
  8. Brouillet E, Chavoix C, de la Sayette V, Hantraye P, Kunimoto M, Khalili-Varasteh M, Guibert B, Fournier D, Dodd RH, Naquet R (1989) Anticonvulsant activity of the diaryltriazine, LY81067: studies using electroencephalographic recording and positron emission tomography. Neuropharmacology 28:351–358PubMedCrossRefGoogle Scholar
  9. Brown JL, Hunsperger RW, Rosvold HE (1969) Defence, attack, and flight elicited by electrical stimulation of the hypothalamus of the cat. Exp Brain Res 8:113–129PubMedGoogle Scholar
  10. Brutkowski D, Dabrowska J (1963) Disinhibition after prefrontal lesions as a function of duration of intertrial intervals. Science 139:505–506PubMedCrossRefGoogle Scholar
  11. Brutkowski S (1965) Functions of prefrontal cortex in animals. Physiol Rev 45:721–746PubMedGoogle Scholar
  12. Burns R, Chiueh C, Markey S, Ebert M, Jacobwitz D, Kopin I (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. Proc Natl Acad Sci U S A 80:4546–4550PubMedCrossRefGoogle Scholar
  13. Cidis MC, Drevets WC, Price JC, Mathis CA, Lopresti B, Greer PJ, Villemagne VL, Holt D, Mason NS, Houck PR, Reynolds CF III, DeKosky ST (2001) Gender-specific aging effects on the serotonin 1A receptor. Brain Res 895:9–17CrossRefGoogle Scholar
  14. Cumming P, Danielsen EH, Vafaee M, Falborg L, Steffensen E, Sorensen JC, Gillings N, Bender D, Marthi K, Andersen F, Munk O, Smith D, Moller A, Gjedde A (2001) Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts. Acta Neurol Scand 103:309–315PubMedCrossRefGoogle Scholar
  15. De la Sayette V, Chavoix C, Brouillet E, Hantraye P, Kunimoto M, Khalili-Varasteh M, Guibert B, Prenant C, Maziere M (1991) In vivo benzodiazepine receptor occupancy by CL 218,872 visualized by positron emission tomography in the brain of the living baboon: modulation by GABAergic transmission and relation with anticonvulsant activity. Exp Brain Res 83:397–402PubMedCrossRefGoogle Scholar
  16. Dewey SL, Smith GS, Logan J, Brodie JD, Yu DW, Ferrieri RA, King PT, MacGregor RR, Martin TP, Wolf AP (1992) GABAergic inhibition of endogenous dopamine release measured in vivo with HC-raclopride and positron emission tomography. J Neurosci 12:3773–3780PubMedGoogle Scholar
  17. Ding Y, Fowler JS, Volkow ND, Dewey S, Wang G, Logan J, Gatley SG, Pappas N (1997) Chiral drugs: comparison of the pharmacokinetics of (HC)d-threo and 1-threo-methylphenidate in the human and baboon brain. Psychopharmacology (Berl) 131:71–78CrossRefGoogle Scholar
  18. Doudet DJ, Hoden JE, Jivan S, McGeer E, Wyatt RJ (2000) In vivo PET studies of the dopamine D2 receptors in rhesus monkeys with long-term MPTP-induced parkinsonism. Synapse 38: 105–113PubMedCrossRefGoogle Scholar
  19. Dougherty D, Alpert N, Rauch S, Fischman A (2001) In vivo neuroreceptor imaging techniques in psychiatric drug development. In: Dougherty D, Rauch S (eds) Psychiatric neuroimaging research, contemporary strategies. American Psychiatric Publishing, Washington DC, pp 193–205Google Scholar
  20. Eberling JL, Roberts JA, Rapp PR, Tuszynski MH, Jagust WJ (1997) Cerebral glucose metabolism and memory in aged rhesus macaques. Neurobiol Aging 18:437–443CrossRefGoogle Scholar
  21. Eberling JL, Bankiewicz KS, Pivirotto P, Bringas J, Chen K, Nowotnik DP, Steiner JP, Budinger TF, Jagust WJ (1999) Dopamine transporter loss and clinical changes in MPTP-lesioned primates. Brain Res 832:184–187PubMedCrossRefGoogle Scholar
  22. Fang P, Wu CY, Liu ZG, Wan WX, Wang TS, Chen SD, Chen ZP, Zhou X (2000) The preclinical pharmacologic study of dopamine transporter imaging agent [99mTc]TRODAT-l. Nucl Med Biol 27:69–75PubMedCrossRefGoogle Scholar
  23. Fink G, Sumner BE, Rosie R, Grace O, Quinn JP (1996) Estrogen control of central neurotransmission: effect on mood, mental state, and memory. Cell Mol Neurobiol 16:325–344PubMedCrossRefGoogle Scholar
  24. Franz S (1902) On the functions of the cerebrum. I. The frontal lobes in relation to the production and retention of simple sensory-motor habits. Am J Physiol 8:1–22Google Scholar
  25. Franz S (1907) On the function of the cerebrum: the frontal lobes. Arch Psychol 2:1–64Google Scholar
  26. Fuster J (1997) Animal neuropsychology. In: Fuster J (ed) The prefrontal cortex: anatomy, physiology and neuropsychology of the frontal lobe. Lippincott-Raven, Philadelphia, pp 66–101Google Scholar
  27. Galynker I, Schlyer DJ, Dewey SL, Fowler JS, Logan J, Gatley SJ, MacGregor RR, Ferrieri RA, Holland MJ, Brodie J, Simon E, Wolf AP (1996) Opioid receptor imaging and displacement studies with [6-O-[11C] methyl]buprenorphine in baboon brain. Nucl Med Biol 23:325–331PubMedCrossRefGoogle Scholar
  28. Ginovart N, Farde L, Halldin C, Swahn CG (1999) Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates. Synapse 31:154–162PubMedCrossRefGoogle Scholar
  29. Ginovart N, Wilson AA, Meyer JH, Hussey D, Houle S (2003) [11C]-DASB, a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter: PET characterization and evaluation in cats. Synapse 47:123–133PubMedCrossRefGoogle Scholar
  30. Harada N, Nishiyama S, Satoh K, Fukumoto D, Kakiuchi T, Tsukada H (2002) Age-related changes in the striatal dopaminergic system in the living brain: a multiparametric PET study in conscious monkeys. Synapse 45:38–45PubMedCrossRefGoogle Scholar
  31. Harvey DC, Lacan G, Tanious SP, Melega WP (2000) Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss. Brain Res 871:259–270PubMedCrossRefGoogle Scholar
  32. Heinz A, Higley JD, Gorey JG, Saunders RC, Jones DW, Hommer D, Zajicek K, Suomi SJ, Lesch KP, Weinberger DR, Linnoila M (1998) In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates. Am J Psychiatry 155: 1023–1028PubMedGoogle Scholar
  33. Heinz A, Jones DW, Gorey JG, Bennet A, Suomi SJ, Weinberger DR, Higley JD (2003) Serotonin transporter availability correlates with alcohol intake in non-human primates. Mol Psychiatry 8:231–234PubMedCrossRefGoogle Scholar
  34. Heiss WD, Graf R, Fujita T, Ohta K, Bauer B, Lottgen J, Wienhard K (1997) Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats. Stroke 28:2045–2051CrossRefGoogle Scholar
  35. Higley JD, Linnoila M (1997) Low central nervous system serotonergic activity is traitlike and correlates with impulsive behavior: a nonhuman primate model investigating genetic and environmental influences on neurotransmission. Ann N Y Acad Sci 836:39–57CrossRefGoogle Scholar
  36. Howell LL, Hoffman JM, Votaw JR, Landrum AM, Wilcox KM, Lindsey KP (2002) Cocaine-induced brain activation determined by positron emission tomography neuroimaging in conscious rhesus monkeys. Psychopharmacology (Berl) 159:154–160CrossRefGoogle Scholar
  37. Jacobson I, Sandberg M, Mori S (1985) Mass transfer in brain dialysis devices: a new method for the estimation of extracellular amino acids concentration. J Neurosci Meth 15:263–268CrossRefGoogle Scholar
  38. Johnson TN, Rosvold HE, Galkin TW, Goldman PS (1976) Postnatal maturation of subcortical projections from the prefrontal cortex in the rhesus monkey. J Comp Neurol 166:427–443PubMedCrossRefGoogle Scholar
  39. Joseph R (1996) The limbic system. Neuropsychiatry, neuropsychology, and clinical neuro-science. Williams and Wilkins, Baltimore, pp 161–205Google Scholar
  40. Kakiuchi T, Nishiyama S, Sato K, Ohba H, Nakanishi S, Tsukada H (2000) Age-related reduction of [11C] MDL 100,907 binding to central 5-HT2A receptors: PET study on the conscious monkey brain. Brain Res 883:135–142PubMedCrossRefGoogle Scholar
  41. Kakiuchi T, Ohba H, Nishiyama S, Sato K, Harada N, Nakanishi S, Tsukada H (2001) Age-related changes in muscarinic cholinergic receptors in the living brain: a PET study using N-[11C]methyl-4-piperidyl benzilate combined with cerebral blood flow measurement in conscious monkeys. Brain Res 916:22–31PubMedCrossRefGoogle Scholar
  42. Kassiou M, Eberl S, Meikle SR, Birrell A, Constable C, Fulham MJ, Wong DF, Musachio JL (2001) In vivo imaging of nicotinic receptor upregulation following chronic (−)-nicotinic treatment in baboon using SPECT. Nucl Med Biol 28:165–175PubMedCrossRefGoogle Scholar
  43. Kavoussi R, Armstead P, Coccaro E (1997) The neurobiology of impulsive aggression. Psychiatr Clin North Am 20:395–403CrossRefGoogle Scholar
  44. Kito G, Nishimura A, Susumu T, Nagata R, Kuge Y, Yokota C, Minematsu K (2001) Experimental thromboembolic stroke in cynomolgus monkey. J Neurosci Methods 105:45–53PubMedCrossRefGoogle Scholar
  45. Kuge Y, Kawashima H, Minematsu K, Hasegawa Y, Yamaguchi T, Miyake Y, Hashimoto T, Imanishi M, Shiomi M, Tamaki N, Hashimoto N (2000) [1–11C]Octanoate as a PET tracer for studying ischemic stroke: evaluation in a canine model of thromboembolic stroke with positron emission tomography. Biol Pharm Bull 23:984–988PubMedCrossRefGoogle Scholar
  46. Kuge Y, Yokota C, Tagaya M, Hasegawa Y, Nishimura A, Kito G, Tamaki N, Hashimoto N, Yamaguchi T, Minematsu K (2001) Serial changes in cerebral blood flow and flow-metabolism uncoupling in primates with acute thromboembolic stroke. J Cereb Blood Flow Metab 21:202–210PubMedCrossRefGoogle Scholar
  47. Kurokawa K, Jibiki I, Matsuda H, Fukushima T, Tsuji S, Yamaguchi N, Hisada K (1994) Comparison of benzodiazepine receptor and regional cerebral blood flow imaging of epileptiform foci in hippocampal kindled rabbits: a study with in vivo double tracer autoradiography using 1251-iomazenil and 99mTc-HMPAO. Brain Res 642:303–310PubMedCrossRefGoogle Scholar
  48. Laruelle M, Iyer RN, al Tikriti MS, Zea-Ponce Y, Malison R, Zoghbi SS, Baldwin RM, Kung HF, Charney DS, Hoffer PB, Innis RB, Bradberry CW (1997) Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates. Synapse 25:1–14CrossRefGoogle Scholar
  49. Lawicka W (1972) Proreal syndrome in dogs. Acta Neurobiol Exp (Warsz) 32:261–276Google Scholar
  50. Leveille J, Demonceau G, Walovitch RC (1992) Intrasubject comparison between technetium-99m-ECD and technetium-99m-HMPAO in healthy human subjects. J Nucl Med 33:480–484PubMedGoogle Scholar
  51. Lu NZ, Eshleman AJ, Janowsky A, Bethea CL (2003) Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques(*). Mol Psychiatry 8:353–360PubMedCrossRefGoogle Scholar
  52. Ma KH, Huang WS, Chen CH, Lin SZ, Wey SP, Ting G, Wang SD, Liu HW, Liu JC (2002) Dual SPECT of dopamine system using [99mTc]TRODAT-l and [123I]IBZM in normal and 6-OHDA-lesioned Formosan rock monkeys. Nucl Med Biol 29:561–567PubMedCrossRefGoogle Scholar
  53. Melega WP, Lacan G, Desalles AA, Phelps ME (2000) Long-term methamphetamine-induced decreases of [11C] WIN 35,428 binding in striatum are reduced by GDNF: PET studies in the vervet monkey. Synapse 35:243–249PubMedCrossRefGoogle Scholar
  54. Melega WP, Raleigh MJ, Stout DB, Lacan G, Huang SC, Phelps ME (1997) Recovery of striatal dopamine function after acute amphetamine and methamphetamine-induced neurotoxicity in the vervet monkey. Brain Res 766:113–120CrossRefGoogle Scholar
  55. Mishkin M, Vest B, Waxier M, Rosvold H (1969) A re-examination of the effects of frontal lesions on object alternation. Neuropsychologia 7:357–363CrossRefGoogle Scholar
  56. Moore AH, Hovda DA, Cherry SR, Villablanca JP, Pollack DB, Phelps ME (2000) Dynamic changes in cerebral glucose metabolism in conscious infant monkeys during the first year of life as measured by positron emission tomography. Brain Res Dev Brain Res 120:141–150PubMedCrossRefGoogle Scholar
  57. Mukherjee J, Christian BT, Narayanan TK, Shi B, Mantil J (2001) Evaluation of dopamine D-2 receptor occupancy by clozapine, risperidone, and haloperidol in vivo in the rodent and non-human primate brain using 18F-fallypride. Neuropsychopharmacology 25:476–488PubMedCrossRefGoogle Scholar
  58. Myers R (1972) Role of prefrontal and anterior temporal cortex in social behavior and affect in monkeys. Acta Neurobiol Exp 32:567–579Google Scholar
  59. Noda A, Ohba H, Kakiuchi T, Futatsubashi M, Tsukada H, Nishimura S (2002) Age-related changes in cerebral blood flow and glucose metabolism in conscious rhesus monkeys. Brain Res 936:76–81PubMedCrossRefGoogle Scholar
  60. Noda A, Takamatsu H, Matsuoka N, Koyama S, Tsukada H, Nishimura S (2003) Effect of FK960, an anti-dementia drug with a novel mechanism of action, on regional cerebral blood flow and glucose metabolism in aged rhesus macaques studied with positron emission tomography. Pharmacol Exp Ther 306:213–217CrossRefGoogle Scholar
  61. Oquendo MA, Mann JJ (2000) The biology of impulsivity and suicidality. Psychiatr Clin North Am 23:11–25PubMedCrossRefGoogle Scholar
  62. Ossowska K, Lorenc-Koci E, Wolfarth S (1994) Antiparkinsonian action of MK-801 on the reserpine-induced rigidity: a mechanomyographic analysis. J Neural Transm Park Dis Dement Sect 7:143–152PubMedCrossRefGoogle Scholar
  63. Peremans K, Audenaert K, Coopman F, Jacobs F, Blanckaert P, Verschooten F, Van Bree H, Van Heeringen C, Mertens J, Slegers G, Dierckx R (2002) Effects of aging on brain perfusion and serotonin-2A receptor binding in the normal canine brain measured with single photon emission tomography. Prog Neuro Psychopharmacol Biol Psychiatry 26:1393–1404CrossRefGoogle Scholar
  64. Poyot T, Conde F, Gregoire MC, Frouin V, Coulon C, Fuseau C, Hinnen F, Dolle F, Hantraye P, Bottlaender M (2001) Anatomic and biochemical correlates of the dopamine transporter ligand 11C-PE2I in normal and parkinsonian primates: comparison with 6-[18F]fluoro-l-dopa. J Cereb Blood Flow Metab 21:782–792PubMedCrossRefGoogle Scholar
  65. Quintana J, Fuster JM (1993) Spatial and temporal factors in the role of prefrontal and parietal cortex in visuomotor integration. Cereb Cortex 3:122–132PubMedCrossRefGoogle Scholar
  66. Reisner IR, Mann JJ, Stanley M, Huang Y, Houpt KA (1996) Comparison of cerebrospinal fluid monoamine metabolite levels in dominant-aggressive and non-aggressive dogs. Brain Res 714:57–64PubMedCrossRefGoogle Scholar
  67. Reneman L, Booij J, Habraken JB, de Bruin K, Hatzidimitriou G, Den Heeten GJ, Ricaurte GA (2002) Validity of [123I]beta-CIT SPECT in detecting MDMA-induced serotonergic neurotoxicity. Synapse 46:199–205PubMedCrossRefGoogle Scholar
  68. Rosvold HE (1972) The frontal lobe system: cortical-subcortical interrelationships. Acta Neurobiol Exp (Warsz) 32:439–460Google Scholar
  69. Roy CS, Sherrington CS (1890)On the regulation of the blood supply of the brain. J Physiol 11: 85–108PubMedGoogle Scholar
  70. Scheffel U, Szabo Z, Mathews WB, Finley PA, Dannals RF, Ravert HT, Szabo K, Yuan J, Ricaurte GA (1998) In vivo detection of short-and long-term MDMA neurotoxicity — a positron emission tomography study in the living baboon brain. Synapse 29:183–192PubMedCrossRefGoogle Scholar
  71. Sette G, Baron JC, Young AR, Miyazawa H, Tillet I, Barre L, Travere JM, Derlon JM, MacKenzie ET (1993) In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anesthetized baboon. Stroke 24:2046–2057PubMedCrossRefGoogle Scholar
  72. Shindy WW, Posley KA, Fuster JM (1994) Reversible deficit in haptic delay tasks from cooling prefrontal cortex. Cereb Cortex 4:443–450PubMedCrossRefGoogle Scholar
  73. Shiue CY, Shiue GG, Cornish KG, O’Rourke MF (1995) PET study of the distribution of [HC]fluoxetine in a monkey brain. Nucl Med Biol 22:613–616PubMedCrossRefGoogle Scholar
  74. Smith DF, Poulsen PH, Ishizu K, Sakoh M, Hansen SB, Gee AD, Bender D, Gjedde A (1998) Quantitative PET analysis of regional cerebral blood flow and glucose and oxygen metabolism in response to fenfluramine in living porcine brain. J Neurosci Methods 86:17–23PubMedCrossRefGoogle Scholar
  75. Smith DF, Gee AD, Hansen SB, Moldt P, Nielsen EO, Scheel-Kruger J, Gjedde A (1999) Uptake and distribution of a new SSRI, NS2381, studied by PET in living porcine brain. Eur Neuropsy-chopharmacol 9:351–359CrossRefGoogle Scholar
  76. Stamm J, Rosen S (1973)The locus and crucial time of implication of prefrontal cortex in the delayed response task. In: Pribram K, Luria A (eds) Psychophysiology of the frontal lobes. Academic, New York, pp 139–153Google Scholar
  77. Suhara T, Okauchi T, Sudo Y, Takano A, Kawabe K, Maeda J, Kapur S (2002) Clozapine can induce high dopamine D(2) receptor occupancy in vivo. Psychopharmacology (Berl) 160:107–112CrossRefGoogle Scholar
  78. Taffe MA, Weed MR, Davis S, Huitron-Resendiz S, Schroeder R, Parsons LH, Henriksen SJ, Gold LH (2001) Functional consequences of repeated (+/−)3,4-methylenedioxymethamphetamine (MDMA) treatment in rhesus monkeys. Neuropsychopharmacology 24:230–239PubMedCrossRefGoogle Scholar
  79. Tang A, Bungay P, Gonzales R (2003) Characterization of probe and tissue factors that influence interpretation of quantitative microdialysis experiments for dopamine. J Neurosci Methods 126:1–11PubMedCrossRefGoogle Scholar
  80. Toyama H, Matsumura K, Nakashima H, Takeda K, Takeuchi A, Koga S, Yoshida T, Ichise M (1998) Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model. Ann Nucl Med 12:267–273PubMedCrossRefGoogle Scholar
  81. Tsukada H, Nishiyama S, Kakiuchi T, Ohba H, Sato K, Harada N (1999a) Is synaptic dopamine concentration the exclusive factor which alters the in vivo binding of [HC]raclopride? PET studies combined with microdialysis in conscious monkeys. Brain Res 841:160–169PubMedCrossRefGoogle Scholar
  82. Tsukada H, Yamazaki S, Noda A, Inoue T, Matsuoka N, Kakiuchi T, Nishiyama S, Nishimura S (1999b) FK960 [N-(4-acetyl-l-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, restores the regional cerebral blood flow response abolished by scopolamine but not by HA-966: a positron emission tomography study with unanesthetized rhesus monkeys. Brain Res 832:118–123PubMedCrossRefGoogle Scholar
  83. Tsukada H, Harada N, Nishiyama S, Ohba H, Kakiuchi T (2000a) Cholinergic neuronal modulation alters dopamine D2 receptor availability in vivo by regulating receptor affinity induced by facilitated synaptic dopamine turnover: positron emission tomography studies with microdialysis in the conscious monkey brain. J Neurosci 20:7067–7073PubMedGoogle Scholar
  84. Tsukada H, Harada N, Nishiyama S, Ohba H, Sato K, Fukumoto D, Kakiuchi T (2000b) 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 27:95–103CrossRefGoogle Scholar
  85. Tsukada H, Kakiuchi T, Fukumoto D, Nishiyama S, Koga K (2000c) Docosahexaenoic acid (DHA) improves the age-related impairment of the coupling mechanism between neuronal activation and functional cerebral blood flow response: a PET study in conscious monkeys. Brain Res 862:180–186PubMedCrossRefGoogle Scholar
  86. Tsukada H, Kakiuchi T, Nishiyama S, Ohba H, Harada N (2001a) Effects of aging on 5-HT(1 A) receptors and their functional response to 5-HT(la) agonist in the living brain: PET study with [carbonyl-11C] WAY-100635 in conscious monkeys. Synapse 42:242–251PubMedCrossRefGoogle Scholar
  87. Tsukada H, Kakiuchi T, Nishiyama S, Ohba H, Sato K, Harada N, Takahashi K (2001b) Age differences in muscarinic cholinergic receptors assayed with (+)N-[11C]methyl-3-piperidyl ben-zilate in the brains of the conscious monkeys. Synapse 41:248–257PubMedCrossRefGoogle Scholar
  88. Tsukada H, Nishiyama S, Kakiuchi T, Ohba H, Sato K, Harada N (2001c) Ketamine alters the availability of striatal dopamine transporter as measured by [11C]beta-CFT and [HC]beta-CIT-FE in the monkey brain. Synapse 42:273–280PubMedCrossRefGoogle Scholar
  89. Tsukada H, Miyasato K, Kakiuchi T, Nishiyama S, Harada N, Domino EF (2002) Comparative effects of methamphetamine and nicotine on the striatal [HC]raclopride binding in unanesthetized monkeys. Synapse 45:207–212PubMedCrossRefGoogle Scholar
  90. Villemagne V, Yuan J, Wong DF, Dannals RF, Hatzidimitriou G, Mathews WB, Ravert HT, Musa-chio J, McCann UD, Ricaurte GA (1998) Brain dopamine neurotoxicity in baboons treated with doses of methamphetamine comparable to those recreationally abused by humans: evidence from [11C]WIN-35,428 positron emission tomography studies and direct in vitro determinations. J Neurosci 18:419–427PubMedGoogle Scholar
  91. Wadenberg ML, Kapur S, Soliman A, Jones C, Vaccarino F (2000) Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in rats. Psychopharmacology (Berl) 150:422–429CrossRefGoogle Scholar
  92. Warren J (1964) The behavior of carnivores and primates with lesions in the prefrontal cortex. In: Warren J, Akert K (eds) The frontal granular cortex and behavior. McGraw-Hill, New York, pp 168–191Google Scholar
  93. Westerink B (1995) Brain microdialysis and its application for the study of animal behaviour. Be-hav Brain Res 70:103–124CrossRefGoogle Scholar
  94. Wilcox K, Lindsey K, Votaw J, Goodman M, Martarello L, Carroll F, Howell L (2002) Self-administration of cocaine and the cocaine analog RTI-113: relationship to dopamine transporter occupancy determined by PET neuroimaging in rhesus monkeys. Synapse 43:78–85PubMedCrossRefGoogle Scholar
  95. Zouakia A, Guilloteau D, Zimmer L, Besnard JC, Chalon S (1997) Evolution of dopamine receptors in the rat after neonatal hypoxia-ischemia: autoradiographic studies. Life Sci 60:151–162CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Kathelijne Peremans
    • 1
  • Kurt Audenaert
    • 2
  • F. Verschooten
    • 3
  • Andreas Otte
    • 4
  • Guido Slegers
    • 5
  • Rudi Dierckx
    • 4
  1. 1.Department of Medical ImagingFaculty of Veterinary MedicineMerelbekeBelgium
  2. 2.Department of Psychiatry and Medical PsychologyUniversity Hospital GhentGentBelgium
  3. 3.Department of Medical Imaging, Faculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
  4. 4.Division of Nuclear MedicineUniversity Hospital GhentGentBelgium
  5. 5.Laboratory for Radiopharmacy, Faculty of Pharmaceutical SciencesGhent UniversityGentBelgium

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