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Measuring Dopamine Synaptic Transmission with Molecular Imaging and Pharmacological Challenges: The State of the Art

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Molecular Imaging in the Clinical Neurosciences

Part of the book series: Neuromethods ((NM,volume 71))

Abstract

Positron Emission Tomography (PET) and Single Photon Emission Computerized Tomography (SPECT) imaging can be applied to measure acute fluctuations in endogenous dopamine (DA) in the living human brain, as captured by opposite changes in D2 receptor ligand in vivo binding. This application of neuroreceptor imaging provides a dynamic assessment of neurotransmission that is very informative to our understanding of the role of DA in health and disease. This chapter reviews briefly the imaging results of endogenous competition studies at D2 receptors obtained in nonhuman primates, healthy subjects, and subjects with neuropsychiatric conditions. This review is followed by a discussion of nature and properties of the interactive processes between DA and D2 receptor binding agents that enable this imaging technique. The original occupancy model proposed that changes in radiotracer binding potential (BP) are directly caused by changes in occupancy of D2 receptors by DA and by classical binding competition. A number of experimental data support this model. The evidence that manipulation of DA synaptic levels induce change in the binding potential (BP) of most D2 radiotracers (antagonists and agonists), irrespective of their affinity, is unequivocal. The fact that these changes in BP are mediated by changes in DA synaptic concentration is well documented. The quantitative relationship between changes in extracellular DA and changes in BP has been established. The observation that the in vivo binding of radiolabeled agonists is more vulnerable than that of antagonists to changes in endogenous DA also support the occupancy model. On the other hand, the amphetamine-induced changes in the BP of D2 receptor supports last longer than amphetamine-induced changes in DA extracellular concentration and that the behavioral and physiological effects of amphetamine. Recent data strongly suggest that DA mediated internalization of D2 receptors is involved in the late phase of the radioligands BP reduction. A general model is proposed, in which the early reduction in BP is caused by binding competition, while the later phase is due to decrease affinity of D2 receptor radiotracers to internalized D2 receptors.

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References

  1. Friedman AM et al (1984) Measurements in vivo of parameters of the dopamine system. Ann Neurol 15(Suppl):S66–76

    PubMed  Google Scholar 

  2. Leysen JE, Gommeren W, Laduron PM (1978) Spiperone: a ligand of choice for neuroleptic receptors. 1. Kinetics and characteristics of in vitro binding. Biochem Pharmacol 27(3):307–16

    PubMed  CAS  Google Scholar 

  3. Lyon RA et al (1986) 3 H-3-N-methylspiperone labels D2 dopamine receptors in basal ganglia and S2 serotonin receptors in cerebral cortex. J Neurosci 6(10):2941–9

    PubMed  CAS  Google Scholar 

  4. Wagner H Jr et al (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221(4617):1264–6

    PubMed  CAS  Google Scholar 

  5. Ehrin E et al (1985) Preparation of 11 C-labelled Raclopride, a new potent dopamine receptor antagonist: preliminary PET studies of cerebral dopamine receptors in the monkey. Int J Appl Radiat Isot 36(4):269–73

    PubMed  CAS  Google Scholar 

  6. Kohler C et al (1985) Specific in vitro and in vivo binding of 3 H-raclopride. A potent substituted benzamide drug with high affinity for dopamine D-2 receptors in the rat brain. Biochem Pharmacol 34(13):2251–9

    PubMed  CAS  Google Scholar 

  7. Kung HF et al (1988) Preparation and biodistribution of [125I]IBZM: a potential CNS D-2 dopamine receptor imaging agent. Nucl Med Biol 15(2):195–201

    CAS  Google Scholar 

  8. Innis RB et al (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27:1533–39

    PubMed  CAS  Google Scholar 

  9. Dewey SL et al (1990) Positron emission tomography (PET) studies of dopamine/cholinergic interaction in the baboon brain. Synapse 6:321–327

    PubMed  CAS  Google Scholar 

  10. Logan J et al (1991) Effects of endogenous dopamine on measures of [18 F]N-methylspiroperidol binding in the basal ganglia: comparison of simulations and experimental results from PET studies in baboons. Synapse 9(3):195–207

    PubMed  CAS  Google Scholar 

  11. Dewey SL et al (1991) Amphetamine induced decrease in [18 F]-N-methylspiperidol binding in the baboon brain using positron emission tomography (PET). Synapse 7:324–327

    PubMed  CAS  Google Scholar 

  12. Hartvig P et al (1997) Amphetamine effects on dopamine release and synthesis rate studied in the Rhesus monkey brain by positron emission tomography. J Neural Transm 104(4–5):329–339

    PubMed  CAS  Google Scholar 

  13. Laruelle M (2000) Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 20(3):423–51

    PubMed  CAS  Google Scholar 

  14. Villemagne VL et al (1999) GBR12909 attenuates amphetamine-induced striatal dopamine release as measured by [(11)C]raclopride continuous infusion PET scans. Synapse 33(4):268–273

    PubMed  CAS  Google Scholar 

  15. Dewey SL et al (1993) Striatal binding of the PET ligand 11 C-raclopride is altered by drugs that modify synaptic dopamine levels. Synapse 13(4):350–6

    PubMed  CAS  Google Scholar 

  16. Carson RE et al (1997) Quantification of amphetamine-induced changes in [C-11]raclopride binding with continuous infusion. J Cereb Blood Flow Metab 17(4):437–447

    PubMed  CAS  Google Scholar 

  17. Ginovart N et al (1998) Effect of anesthetics and evoked dopamine release on [11 C]raclopride binding in the cat striatum. Neuroimage 7:A7

    Google Scholar 

  18. Ginovart N et al (1999) Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates. Synapse 31(2):154–62

    PubMed  CAS  Google Scholar 

  19. Volkow ND et al (1999) Comparable changes in synaptic dopamine induced by methylphenidate and by cocaine in the baboon brain. Synapse 31(1):59–66

    PubMed  CAS  Google Scholar 

  20. Abi-Dargham A et al (1999) PET studies of binding competition between endogenous dopamine and the D1 radiotracer [11 C]NNC 756. Synapse 32(2):93–109

    PubMed  CAS  Google Scholar 

  21. Price J et al (1998) PET measurement of endogenous neurotransmitter activity using high and low affinity radiotracers. In: Carson R, Daube-Witherspoon ME, Herscovitch P (eds) Quantitative functional brain imaging with positron emission tomography. Academic, San Diego, pp 441–448

    Google Scholar 

  22. Ginovart N et al (1997) Effect of reserpine-induced depletion of synaptic dopamine on [C-11]raclopride binding to D-2-dopamine receptors in the monkey brain. Synapse 25(4):321–325

    PubMed  CAS  Google Scholar 

  23. Gatley SJ et al (1995) Sensitivity of striatal [11 C]cocaine binding to decreases in synaptic dopamine. Synapse 20(2):137–44

    PubMed  CAS  Google Scholar 

  24. Innis RB et al (1992) Amphetamine-stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in non-human primates. Synapse 10:177–184

    PubMed  CAS  Google Scholar 

  25. Laruelle M et al (1997) Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates. Synapse 25:1–14

    PubMed  CAS  Google Scholar 

  26. Mach RH et al (1997) Use of positron emission tomography to study the dynamics of psychostimulant-induced dopamine release. Pharmacol Biochem Behav 57(3):477–486

    PubMed  CAS  Google Scholar 

  27. Kessler RM et al (1993) Evaluation of 5-[18 F]fluoropropylepidepride as a potential PET radioligand for imaging dopamine D2 receptors. Synapse 15(3):169–76

    PubMed  CAS  Google Scholar 

  28. Mukherjee J et al (1997) Evaluation of d-amphetamine effects on the binding of dopamine D-2 receptor radioligand, F-18-fallypride in nonhuman primates using positron emission tomography. Synapse 27(1):1–13

    PubMed  CAS  Google Scholar 

  29. Narendran R et al (2005) Measurement of the proportion of D2 receptors configured in state of high affinity for agonists in vivo: a positron emission tomography study using [11 C]N-propyl-norapomorphine and [11 C]raclopride in baboons. J Pharmacol Exp Ther 315(1):80–90

    PubMed  CAS  Google Scholar 

  30. Mukherjee J et al (2005) Measurement of d-amphetamine-induced effects on the binding of dopamine D-2/D-3 receptor radioligand, 18 F-fallypride in extrastriatal brain regions in non-human primates using PET. Brain Res 1032(1–2):77–84

    PubMed  CAS  Google Scholar 

  31. Chou YH, Halldin C, Farde L (2000) Effect of amphetamine on extrastriatal D2 dopamine receptor binding in the primate brain: a PET study. Synapse 38(2):138–43

    PubMed  CAS  Google Scholar 

  32. Narendran R et al (2006) Dopamine (D2/3) receptor agonist positron emission tomography radiotracer [11 C]-(+)-PHNO is a D3 receptor preferring agonist in vivo. Synapse 60(7):485–95

    PubMed  CAS  Google Scholar 

  33. Narendran R et al (2004) In vivo vulnerability to competition by endogenous dopamine: comparison of the D2 receptor agonist radiotracer (-)-N-[11 C]propyl-norapomorphine ([11 C]NPA) with the D2 receptor antagonist radiotracer [11 C]-raclopride. Synapse 52(3):188–208

    PubMed  CAS  Google Scholar 

  34. Seneca N et al (2006) Effect of amphetamine on dopamine D2 receptor binding in nonhuman primate brain: a comparison of the agonist radioligand [11 C]MNPA and antagonist [11 C]raclopride. Synapse 59(5):260–9

    PubMed  CAS  Google Scholar 

  35. Ginovart N et al (2006) Binding characteristics and sensitivity to endogenous dopamine of [11 C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography. J Neurochem 97(4):1089–103

    PubMed  CAS  Google Scholar 

  36. Tokunaga M et al (2009) Neuroimaging and physiological evidence for involvement of glutamatergic transmission in regulation of the striatal dopaminergic system. J Neurosci 29(6):1887–96

    PubMed  CAS  Google Scholar 

  37. Farde L et al (1992) Positron emission tomography analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry 49:538–544

    PubMed  CAS  Google Scholar 

  38. Volkow ND et al (1994) Imaging endogenous dopamine competition with [11 C]raclopride in the human brain. Synapse 16:255–262

    PubMed  CAS  Google Scholar 

  39. Laruelle M et al (1995) SPECT imaging of striatal dopamine release after amphetamine challenge. J Nucl Med 36:1182–1190

    PubMed  CAS  Google Scholar 

  40. Booij J et al (1997) Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography. Eur J Nucl Med 24(6):674–677

    PubMed  CAS  Google Scholar 

  41. Breier A et al (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method. Proc Natl Acad Sci USA 94(6):2569–2574

    PubMed  CAS  Google Scholar 

  42. Martinez D et al (2003) Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. J Cereb Blood Flow Metab 23(3):285–300

    PubMed  CAS  Google Scholar 

  43. Cardenas L et al (2004) Oral D-amphetamine causes prolonged displacement of [11 C]raclopride as measured by PET. Synapse 51(1):27–31

    PubMed  CAS  Google Scholar 

  44. Leyton M et al (2002) Amphetamine-induced increases in extracellular dopamine, drug wanting, and novelty seeking: a PET/[11 C]raclopride study in healthy men. Neuropsychopharmacology 27(6):1027–35

    PubMed  CAS  Google Scholar 

  45. Drevets WC et al (2001) Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol Psychiatry 49(2):81–96

    PubMed  CAS  Google Scholar 

  46. Watabe H et al (2000) Measurement of dopamine release with continuous infusion of [11 C]raclopride: optimization and signal-to-noise considerations. J Nucl Med 41(3):522–30

    PubMed  CAS  Google Scholar 

  47. Carson RE et al (2001) Amphetamine-induced dopamine release: duration of action assessed with [11 C]raclopride in anesthetized monkeys. In: Gjedde A et al (eds) Physiological imaging of the brain with PET. Academic, San Diego, CA

    Google Scholar 

  48. Oswald LM et al (2005) Relationships among ventral striatal dopamine release, cortisol secretion, and subjective responses to amphetamine. Neuropsychopharmacology 30(4):821–32

    PubMed  CAS  Google Scholar 

  49. Narendran R et al (2010) A comparative evaluation of the dopamine D(2/3) agonist radiotracer [11 C](-)-N-propyl-norapomorphine and antagonist [11 C]raclopride to measure amphetamine-induced dopamine release in the human striatum. J Pharmacol Exp Ther 333(2):533–9

    PubMed  CAS  Google Scholar 

  50. Oswald LM et al (2007) Impulsivity and chronic stress are associated with amphetamine-induced striatal dopamine release. Neuroimage 36(1):153–66

    PubMed  Google Scholar 

  51. Volkow ND et al (2002) Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications. Synapse 43(3):181–7

    PubMed  CAS  Google Scholar 

  52. Clatworthy PL et al (2009) Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory. J Neurosci 29(15):4690–6

    PubMed  CAS  Google Scholar 

  53. Munro CA et al (2006) Sex differences in striatal dopamine release in healthy adults. Biol Psychiatry 59(10):966–74

    PubMed  CAS  Google Scholar 

  54. Boileau I, et al. (2003) Sensitization to psychostimulants: a PET/[11 C]-Raclopride study in healthy volunteers. ACNP Annual Meting Abstracts

    Google Scholar 

  55. Kegeles LS et al (1999) Stability of [123I]IBZM SPECT measurement of amphetamine-induced striatal dopamine release in humans. Synapse 31(4):302–8

    PubMed  CAS  Google Scholar 

  56. Abi-Dargham A et al (2003) Dopamine mediation of positive reinforcing effects of amphetamine in stimulant naive healthy volunteers: results from a large cohort. Eur Neuropsychopharmacol 13(6):459–68

    PubMed  CAS  Google Scholar 

  57. Udo de Haes JI et al (2005) Assessment of methylphenidate-induced changes in binding of continuously infused [(11)C]-raclopride in healthy human subjects: correlation with subjective effects. Psychopharmacology (Berl) 183(3):322–30

    CAS  Google Scholar 

  58. Schlaepfer TE et al (1997) PET study of competition between intravenous cocaine and [C-11]raclopride at dopamine receptors in human subjects. Am J Psychiatry 154(9):1209–1213

    PubMed  CAS  Google Scholar 

  59. Leyton M et al (2004) Decreasing amphetamine-induced dopamine release by acute phenylalanine/tyrosine depletion: A PET/[11 C]raclopride study in healthy men. Neuropsychopharmacology 29(2):427–32

    PubMed  CAS  Google Scholar 

  60. Cox SM et al (2011) Effects of lowered serotonin transmission on cocaine-induced striatal dopamine response: PET [11 C]raclopride study in humans. Br J Psychiatry 199:391–397

    PubMed  Google Scholar 

  61. Cox SM et al (2009) Striatal dopamine responses to intranasal cocaine self-administration in humans. Biol Psychiatry 65(10):846–50

    PubMed  CAS  Google Scholar 

  62. Brody AL et al (2004) Smoking-induced ventral striatum dopamine release. Am J Psychiatry 161(7):1211–8

    PubMed  Google Scholar 

  63. Montgomery AJ et al (2007) The effect of nicotine on striatal dopamine release in man: A [11 C]raclopride PET study. Synapse 61(8):637–45

    PubMed  CAS  Google Scholar 

  64. Brody AL et al (2009) Ventral striatal dopamine release in response to smoking a regular vs a denicotinized cigarette. Neuropsychopharmacology 34(2):282–9

    PubMed  CAS  Google Scholar 

  65. Takahashi H et al (2008) Enhanced dopamine release by nicotine in cigarette smokers: a double-blind, randomized, placebo-controlled pilot study. Int J Neuropsychopharmacol 11(3):413–7

    PubMed  CAS  Google Scholar 

  66. Barrett SP et al (2004) The hedonic response to cigarette smoking is proportional to dopamine release in the human striatum as measured by positron emission tomography and [11 C]raclopride. Synapse 54(2):65–71

    PubMed  CAS  Google Scholar 

  67. Marenco S et al (2004) Nicotine-induced dopamine release in primates measured with [11 C]raclopride PET. Neuropsychopharmacology 29(2):259–68

    PubMed  CAS  Google Scholar 

  68. Daglish MR et al (2008) Brain dopamine response in human opioid addiction. Br J Psychiatry 193(1):65–72

    PubMed  Google Scholar 

  69. Boileau I et al (2003) Alcohol promotes dopamine release in the human nucleus accumbens. Synapse 49(4):226–31

    PubMed  CAS  Google Scholar 

  70. Yoder KK et al (2007) Heterogeneous effects of alcohol on dopamine release in the striatum: a PET study. Alcohol Clin Exp Res 31(6):965–73

    PubMed  CAS  Google Scholar 

  71. Urban NB et al (2010) Sex differences in striatal dopamine release in young adults after oral alcohol challenge: a positron emission tomography imaging study with [(1)(1)C]raclopride. Biol Psychiatry 68(8):689–96

    PubMed  CAS  Google Scholar 

  72. Stokes PR et al (2009) Can recreational doses of THC produce significant dopamine release in the human striatum? Neuroimage 48(1):186–90

    PubMed  Google Scholar 

  73. Egerton A et al (2009) Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: an [11 C]raclopride PET study. Neuroimage 50(1):260–6

    PubMed  Google Scholar 

  74. Volkow ND et al (2009) Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. JAMA 301(11):1148–54

    PubMed  CAS  Google Scholar 

  75. Bantick RA, De Vries MH, Grasby PM (2005) The effect of a 5-HT1A receptor agonist on striatal dopamine release. Synapse 57(2):67–75

    PubMed  CAS  Google Scholar 

  76. Smith GS et al (1998) Glutamate modulation of dopamine measured in vivo with positron emission tomography (PET) and 11 C-raclopride in normal human subjects. Neuropsychopharmacology 18(1):18–25

    PubMed  CAS  Google Scholar 

  77. Breier A et al (1998) Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach. Synapse 29(2):142–7

    PubMed  CAS  Google Scholar 

  78. Vollenweider FX et al (2000) Effects of (S)-ketamine on striatal dopamine: a [11 C]raclopride PET study of a model psychosis in humans. J Psychiatr Res 34(1):35–43

    PubMed  CAS  Google Scholar 

  79. Kegeles LS et al (2002) NMDA antagonist effects on striatal dopamine release: positron emission tomography studies in humans. Synapse 43(1):19–29

    PubMed  CAS  Google Scholar 

  80. Aalto S et al (2002) Ketamine does not decrease striatal dopamine D2 receptor binding in man. Psychopharmacology (Berl) 164(4):401–6

    CAS  Google Scholar 

  81. Koepp MJ et al (1998) Evidence for striatal dopamine release during a video game. Nature 393(6682):266–8

    PubMed  CAS  Google Scholar 

  82. Goerendt IK et al (2003) Dopamine release during sequential finger movements in health and Parkinson’s disease: a PET study. Brain 126(Pt 2):312–25

    PubMed  Google Scholar 

  83. Ouchi Y et al (2002) Effect of simple motor performance on regional dopamine release in the striatum in Parkinson disease patients and healthy subjects: a positron emission tomography study. J Cereb Blood Flow Metab 22(6):746–52

    PubMed  CAS  Google Scholar 

  84. de la Fuente-Fernandez R et al (2001) Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease. Science 293(5532):1164–6

    PubMed  Google Scholar 

  85. Boileau I et al (2007) Conditioned dopamine release in humans: a positron emission tomography [11 C]raclopride study with amphetamine. J Neurosci 27(15):3998–4003

    PubMed  CAS  Google Scholar 

  86. Scott DJ et al (2007) Individual differences in reward responding explain placebo-induced expectations and effects. Neuron 55(2):325–36

    PubMed  CAS  Google Scholar 

  87. Scott DJ et al (2008) Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry 65(2):220–31

    PubMed  Google Scholar 

  88. Volkow ND et al (2002) “Nonhedonic” food motivation in humans involves dopamine in the dorsal striatum and methylphenidate amplifies this effect. Synapse 44(3):175–80

    PubMed  CAS  Google Scholar 

  89. Volkow ND et al (2003) Brain dopamine is associated with eating behaviors in humans. Int J Eat Disord 33(2):136–42

    PubMed  Google Scholar 

  90. Small DM, Jones-Gotman M, Dagher A (2003) Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. Neuroimage 19(4):1709–15

    PubMed  Google Scholar 

  91. Scott DJ et al (2007) Time-course of change in [11 C]carfentanil and [11 C]raclopride binding potential after a nonpharmacological challenge. Synapse 61(9):707–14

    PubMed  CAS  Google Scholar 

  92. Montgomery AJ, Mehta MA, Grasby PM (2006) Is psychological stress in man associated with increased striatal dopamine levels?: A [11 C]raclopride PET study. Synapse 60(2):124–31

    PubMed  CAS  Google Scholar 

  93. Soliman A et al (2008) Stress-induced dopamine release in humans at risk of psychosis: a [11 C]raclopride PET study. Neuropsychopharmacology 33(8):2033–41

    PubMed  CAS  Google Scholar 

  94. Pruessner JC et al (2004) Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [11 C]raclopride. J Neurosci 24(11):2825–31

    PubMed  CAS  Google Scholar 

  95. Zald DH et al (2004) Dopamine transmission in the human striatum during monetary reward tasks. J Neurosci 24(17):4105–12

    PubMed  CAS  Google Scholar 

  96. Wong DF et al (2006) Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving. Neuropsychopharmacology 31(12):2716–27

    PubMed  CAS  Google Scholar 

  97. Volkow ND et al (2006) Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci 26(24):6583–8

    PubMed  CAS  Google Scholar 

  98. Salimpoor VN et al (2011) Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nat Neurosci 14(2):257–62

    PubMed  CAS  Google Scholar 

  99. Volkow ND et al (2009) Hyperstimulation of striatal D2 receptors with sleep deprivation: Implications for cognitive impairment. Neuroimage 45(4):1232–40

    PubMed  Google Scholar 

  100. Volkow ND et al (2008) Sleep deprivation decreases binding of [11 C]raclopride to dopamine D2/D3 receptors in the human brain. J Neurosci 28(34):8454–61

    PubMed  CAS  Google Scholar 

  101. Strafella AP et al (2003) Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 126(Pt 12):2609–15

    PubMed  Google Scholar 

  102. Strafella AP et al (2001) Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci 21(15):157

    Google Scholar 

  103. Laruelle M et al (1997) Imaging D-2 receptor occupancy by endogenous dopamine in humans. Neuropsychopharmacology 17(3):162–174

    PubMed  CAS  Google Scholar 

  104. Verhoeff NP et al (2003) Effects of catecholamine depletion on D(2) receptor binding, mood, and attentiveness in humans: a replication study. Pharmacol Biochem Behav 74(2):425–432

    PubMed  CAS  Google Scholar 

  105. Verhoeff NP et al (2002) Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans. Mol Psychiatry 7(3):233

    PubMed  CAS  Google Scholar 

  106. Verhoeff NP et al (2001) A simple method to measure baseline occupancy of neostriatal dopamine D2 receptors by dopamine in vivo in healthy subjects. Neuropsychopharmacology 25:213–223

    PubMed  CAS  Google Scholar 

  107. Kegeles LS et al (2010) Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Arch Gen Psychiatry 67(3):231–9

    PubMed  CAS  Google Scholar 

  108. Abi-Dargham A et al (2000) Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 97(14):8104–8109

    PubMed  CAS  Google Scholar 

  109. Slifstein M et al (2004) Effect of amphetamine on [(18)F]fallypride in vivo binding to D(2) receptors in striatal and extrastriatal regions of the primate brain: Single bolus and bolus plus constant infusion studies. Synapse 54(1):46–63

    PubMed  CAS  Google Scholar 

  110. Cropley VL et al (2008) Small effect of dopamine release and no effect of dopamine depletion on [18 F]fallypride binding in healthy humans. Synapse 62(6):399–408

    PubMed  CAS  Google Scholar 

  111. Riccardi P et al (2006) Amphetamine-induced displacement of [18 F] fallypride in striatum and extrastriatal regions in humans. Neuropsychopharmacology 31(5):1016–26

    PubMed  CAS  Google Scholar 

  112. Narendran R et al (2009) Positron emission tomography imaging of amphetamine-induced dopamine release in the human cortex: a comparative evaluation of the high affinity dopamine D2/3 radiotracers [11 C]FLB 457 and [11 C]fallypride. Synapse 63(6):447–61

    PubMed  CAS  Google Scholar 

  113. Slifstein M et al (2009) Striatal and extrastriatal dopamine release measured with PET and [(18)F] fallypride. Synapse 64(5):350–62

    Google Scholar 

  114. Narendran R et al (2010) Positron emission tomography imaging of dopamine D/receptors in the human cortex with [(1)(1)C]FLB 457: reproducibility studies. Synapse 65(1):35–40

    Google Scholar 

  115. Aalto S et al (2009) The effects of d-amphetamine on extrastriatal dopamine D2/D3 receptors: a randomized, double-blind, placebo-controlled PET study with [11 C]FLB 457 in healthy subjects. Eur J Nucl Med Mol Imaging 36(3):475–83

    PubMed  CAS  Google Scholar 

  116. Montgomery AJ et al (2007) Measurement of methylphenidate-induced change in extrastriatal dopamine concentration using [11 C]FLB 457 PET. J Cereb Blood Flow Metab 27(2):369–77

    PubMed  CAS  Google Scholar 

  117. Frankle WG et al (2010) No effect of dopamine depletion on the binding of the high-affinity D 2/3 radiotracer [11 C]FLB 457 in the human cortex. Synapse 64(12):879–85

    PubMed  CAS  Google Scholar 

  118. Riccardi P et al (2008) Estimation of baseline dopamine D2 receptor occupancy in striatum and extrastriatal regions in humans with positron emission tomography with [18 F] fallypride. Biol Psychiatry 63(2):241–4

    PubMed  CAS  Google Scholar 

  119. Willeit M et al (2008) First human evidence of d-amphetamine induced displacement of a D2/3 agonist radioligand: a [11 C]-(+)-PHNO positron emission tomography study. Neuropsychopharmacology 33(2):279–89

    PubMed  CAS  Google Scholar 

  120. Shotbolt P, et al. (2012) Within-subject comparison of [11 C]-(+)-PHNO and [11 C]Raclopride sensitivity to acute amphetamine challenge in healthy humans. J Cereb Blood Flow Metab 32:127–136

    Google Scholar 

  121. Laruelle M et al (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug free schizophrenic subjects. Proc Natl Acad Sci USA 93:9235–9240

    PubMed  CAS  Google Scholar 

  122. Abi-Dargham A et al (1998) Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 155:761–767

    PubMed  CAS  Google Scholar 

  123. Laruelle M et al (1999) Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol Psychiatry 46(1):56–72

    PubMed  CAS  Google Scholar 

  124. Abi-Dargham A et al (2004) Striatal amphetamine-induced dopamine release in patients with schizotypal personality disorder studied with single photon emission computed tomography and [123I]iodobenzamide. Biol Psychiatry 55(10):1001–6

    PubMed  CAS  Google Scholar 

  125. Kegeles LS et al (2000) Modulation of amphetamine-induced striatal dopamine release by ketamine in humans: implications for schizophrenia. Biol Psychiatry 48(7):627–640

    PubMed  CAS  Google Scholar 

  126. Laruelle M, Kegeles LS, Abi-Dargham A (2003) Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann N Y Acad Sci 1003:138–158

    PubMed  CAS  Google Scholar 

  127. Kegeles LS et al (2010) Striatal and extrastriatal dopamine D2/D3 receptors in schizophrenia evaluated with [18 F]fallypride positron emission tomography. Biol Psychiatry 68(7):634–41

    PubMed  CAS  Google Scholar 

  128. Volkow ND et al (1997) Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 386:830–833

    PubMed  CAS  Google Scholar 

  129. Malison RT, Mechanic KY, Klummp HEA (1999) Reduced amphetamine-stimulated dopamine release in cocaine addicts as measured by [123I]IBZM SPECT. J Nucl Med 40:110P

    Google Scholar 

  130. Martinez D et al (2007) Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. Am J Psychiatry 164(4):622–9

    PubMed  Google Scholar 

  131. Martinez D et al (2009) Lower level of endogenous dopamine in patients with cocaine dependence: findings from PET imaging of D(2)/D(3) receptors following acute dopamine depletion. Am J Psychiatry 166(10):1170–7

    PubMed  Google Scholar 

  132. Volkow ND et al (2007) Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J Neurosci 27(46):12700–6

    PubMed  CAS  Google Scholar 

  133. Martinez D et al (2005) Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry 58(10):779–86

    PubMed  CAS  Google Scholar 

  134. Busto UE et al (2009) Dopaminergic activity in depressed smokers: a positron emission tomography study. Synapse 63(8):681–9

    PubMed  CAS  Google Scholar 

  135. Martinez D, Narendran R (2010) Imaging neurotransmitter release by drugs of abuse. Curr Top Behav Neurosci 3:219–45

    PubMed  Google Scholar 

  136. Piccini P, Pavese N, Brooks DJ (2003) Endogenous dopamine release after pharmacological challenges in Parkinson’s disease. Ann Neurol 53(5):647–53

    PubMed  CAS  Google Scholar 

  137. Koochesfahani KM et al (2006) Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: positron emission tomographic studies. Mov Disord 21(7):970–5

    PubMed  Google Scholar 

  138. Volkow ND et al (2007) Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 64(8):932–40

    PubMed  CAS  Google Scholar 

  139. Singer HS et al (2002) Elevated intrasynaptic dopamine release in Tourette’s syndrome measured by PET. Am J Psychiatry 159(8):1329–36

    PubMed  Google Scholar 

  140. Parsey RV et al (2001) Dopamine D(2) receptor availability and amphetamine-induced dopamine release in unipolar depression. Biol Psychiatry 50(5):313–22

    PubMed  CAS  Google Scholar 

  141. Schneier FR et al (2000) Low dopamine D(2) receptor binding potential in social phobia. Am J Psychiatry 157(3):457–459

    PubMed  CAS  Google Scholar 

  142. Wang GJ et al (2011) Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity (Silver Spring) 19(8):1601–8

    CAS  Google Scholar 

  143. Bailer UF et al (2011) Amphetamine induced dopamine release increases anxiety in individuals recovered from anorexia nervosa. Int J Eat Disord 45:263–71

    PubMed  Google Scholar 

  144. Riccardi P et al (2010) Sex differences in the relationship of regional dopamine release to affect and cognitive function in striatal and extrastriatal regions using positron emission tomography and [(1)F]fallypride. Synapse 65(2):99–102

    Google Scholar 

  145. Egerton A et al (2009) The dopaminergic basis of human behaviors: a review of molecular imaging studies. Neurosci Biobehav Rev 33(7):1109–32

    PubMed  CAS  Google Scholar 

  146. Slifstein M, Laruelle M (2001) Models and methods for derivation of in vivo neuroreceptor parameters with PET and SPECT reversible radiotracers. Nucl Med Biol 28(5):595–608

    PubMed  CAS  Google Scholar 

  147. Guo Q, Brady M, Gunn RN (2009) A biomathematical modeling approach to central nervous system radioligand discovery and development. J Nucl Med 50(10):1715–23

    PubMed  CAS  Google Scholar 

  148. Laruelle M, Slifstein M, Huang Y (2003) Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography. Mol Imaging Biol 5(6):363–75

    PubMed  Google Scholar 

  149. Seeman P, Guan H-C, Niznik HB (1989) Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3 H]raclopride: implications for positron emission tomography of the human brain. Synapse 3:96–97

    PubMed  CAS  Google Scholar 

  150. Cheng Y, Prusoff W (1973) Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 percent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099–3108

    PubMed  CAS  Google Scholar 

  151. Sulzer D et al (1995) Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci 15(5 Pt 2):4102–8

    PubMed  CAS  Google Scholar 

  152. Fischer JF, Cho AK (1979) Chemical release of dopamine from striatal homogenates: evidence for an exchange diffusion model. J Pharmacol Exp Ther 208(2):203–9

    PubMed  CAS  Google Scholar 

  153. Raiteri M et al (1979) Dopamine can be released by two mechanisms differentially affected by the dopamine transport inhibitor nomifensine. J Pharmacol Exp Ther 208(2):195–202

    PubMed  CAS  Google Scholar 

  154. Parker EM, Cubeddu LX (1986) Effects of d-amphetamine and dopamine synthesis inhibitors on dopamine and acetylcholine neurotransmission in the striatum. I. Release in the absence of vesicular transmitter stores. J Pharmacol Exp Ther 237(1):179–92

    PubMed  CAS  Google Scholar 

  155. Simon JR et al (1991) In vitro release of endogenous dopamine from the striatum of the weaver mutant mouse. J Neurochem 57(5):1478–82

    PubMed  CAS  Google Scholar 

  156. Butcher SP et al (1988) Amphetamine-induced dopamine release in rat striatum: an in vivo microdialysis study. J Neurochem 50:346–355

    PubMed  CAS  Google Scholar 

  157. Connor CE, Kuczenski R (1986) Evidence that amphetamine and Na + gradient reversal increase striatal synaptosomal dopamine synthesis through carrier-mediated efflux of dopamine. Biochem Pharmacol 35(18):3123–30

    PubMed  CAS  Google Scholar 

  158. Nash JF, Yamamoto BK (1993) Effect of D-amphetamine on the extracellular concentrations of glutamate and dopamine in iprindole-treated rats. Brain Res 627(1):1–8

    PubMed  CAS  Google Scholar 

  159. Cadoni C et al (1995) Role of vesicular dopamine in the in vivo stimulation of striatal dopamine transmission by amphetamine: evidence from microdialysis and Fos immunohistochemistry. Neuroscience 65(4):1027–39

    PubMed  CAS  Google Scholar 

  160. Sulzer D, Maidment NT, Rayport S (1993) Amphetamine and other weak bases act to promote reverse transport of dopamine in ventral midbrain neurons. J Neurochem 60(2):527–35

    PubMed  CAS  Google Scholar 

  161. Pifl C et al (1995) Mechanism of the dopamine-releasing actions of amphetamine and cocaine: plasmalemmal dopamine transporter versus vesicular monoamine transporter. Mol Pharmacol 47(2):368–373

    PubMed  CAS  Google Scholar 

  162. Florin SM, Kuczenski R, Segal DS (1995) Effects of reserpine on extracellular caudate dopamine and hippocampus norepinephrine responses to amphetamine and cocaine: mechanistic and behavioral considerations. J Pharmacol Exp Ther 274(1):231–41

    PubMed  CAS  Google Scholar 

  163. Dluzen DE, Liu B (1994) The effect of reserpine treatment in vivo upon L-dopa and amphetamine evoked dopamine and DOPAC efflux in vitro from the corpus striatum of male rats. J Neural Transm Gen Sect 95(3):209–22

    PubMed  CAS  Google Scholar 

  164. Schiffer WK et al (2006) Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine. Synapse 59(4):243–51

    PubMed  CAS  Google Scholar 

  165. Sibley DR, De Lean A, Creese I (1982) Anterior pituitary receptors: demonstration of interconvertible high and low affinity states of the D2 dopamine receptor. J Biol Chem 257:6351–6361

    PubMed  CAS  Google Scholar 

  166. Seeman P, Grigoriadis D (1987) Dopamine receptors in brain and periphery. Neurochem Int 10:1–25

    PubMed  CAS  Google Scholar 

  167. Richfield EK, Penney JB, Young AB (1989) Anatomical and affinity state comparisons between dopamine D1 and D2 receptors in the rat central nervous system. Neuroscience 30(3):767–77

    PubMed  CAS  Google Scholar 

  168. Zahniser NR, Molinoff PB (1978) Effect of guanine nucleotides on striatal dopamine receptors. Nature 275(5679):453–5

    PubMed  CAS  Google Scholar 

  169. George SR et al (1985) The functional state of the dopamine receptor in the anterior pituitary is in the high affinity form. Endocrinology 117(2):690–7

    PubMed  CAS  Google Scholar 

  170. Caille I, Dumartin B, Bloch B (1996) Ultrastructural localization of D1 dopamine receptor immunoreactivity in rat striatonigral neurons and its relation with dopaminergic innervation. Brain Res 730(1–2):17–31

    PubMed  CAS  Google Scholar 

  171. Levey AI et al (1993) Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies. Proc Natl Acad Sci USA 90(19):8861–5

    PubMed  CAS  Google Scholar 

  172. Smiley JF et al (1994) D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines. Proc Natl Acad Sci USA 91(12):5720–4

    PubMed  CAS  Google Scholar 

  173. Hersch SM et al (1995) Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents. J Neurosci 15(7 Pt 2):5222–37

    PubMed  CAS  Google Scholar 

  174. Yung KK et al (1995) Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy. Neuroscience 65(3):709–30

    PubMed  CAS  Google Scholar 

  175. Church WH, Justice JB, Byrd LD (1987) Extracellular dopamine in rat striatum following uptake inhibition by cocaine, nomifensine and benztropine. Eur J Pharmacol 139:345–348

    PubMed  CAS  Google Scholar 

  176. Kawagoe KT et al (1992) Regulation of transient dopamine concentration gradients in the microenvironment surrounding nerve terminals in the rat striatum. Neuroscience 51(1):55–64

    PubMed  CAS  Google Scholar 

  177. May LJ (1988) Differentiation of dopamine overflow and uptake processes in the extracellular fluid of the rat caudate nucleus with fast-scan in vivo voltammetry. J Neurochem 51(4):1060–1069

    PubMed  CAS  Google Scholar 

  178. Grace AA (1993) Cortical regulation of subcortical systems and its possible relevance to schizophrenia. J Neural Transm 91:111–134

    CAS  Google Scholar 

  179. Kuhr WG et al (1984) Monitoring the stimulated release of dopamine with in vivo voltammetry. I: Characterization of the response observed in the caudate nucleus of the rat. J Neurochem 43(2):560–9

    PubMed  CAS  Google Scholar 

  180. Kuhr WG, Wightman RM (1986) Real-time measurement of dopamine release in rat brain. Brain Res 381(1):168–71

    PubMed  CAS  Google Scholar 

  181. Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41(1):1–24

    PubMed  CAS  Google Scholar 

  182. Kim SE et al (1998) Nicotine-induced dopamine release evaluated with in vivo 3 H raclopride binding studies: comparison with in vivo dialysis data. J Nucl Med 39:54P

    Google Scholar 

  183. Tsukada H et al (1999) Is synaptic dopamine concentration the exclusive factor which alters the in vivo binding of [11 C]raclopride?: PET studies combined with microdialysis in conscious monkeys. Brain Res 841(1–2):160–9

    PubMed  CAS  Google Scholar 

  184. Richfield EK, Penney JB, Young AB (1989) Anatomical and affinity state comparisons between dopamine D1 and D2 reseptors in the rat central nervous system. Neuroscience 30(3):767–777

    PubMed  CAS  Google Scholar 

  185. Drevets WC et al (1999) PET measures of amphetamine-induced dopamine release in ventral versus dorsal striatum. Neuropsychopharmacology 21(6):694–709

    PubMed  CAS  Google Scholar 

  186. Endres CJ et al (1997) Kinetic modeling of [C-11]raclopride: Combined PET-microdialysis studies. J Cereb Blood Flow Metab 17(9):932–942

    PubMed  CAS  Google Scholar 

  187. Seeman P (1993) Receptor tables. Vol. 2: Drug dissociation constants for neuroreceptors and transporters. Toronto, Canada

    Google Scholar 

  188. Richfield EK, Young AB, Penney JB (1986) Properties of D2 dopamine receptor autoradiography: high percentage of high-affinity agonist sites and increased nucleotide sensitivity in tissue sections. Brain Res 383(1–2):121–8

    PubMed  CAS  Google Scholar 

  189. Rabiner EA et al (2009) In vivo quantification of regional dopamine-D3 receptor binding potential of (+)-PHNO: Studies in non-human primates and transgenic mice. Synapse 63(9):782–93

    PubMed  CAS  Google Scholar 

  190. Tziortzi AC et al (2011) Imaging dopamine receptors in humans with [(11)C]-(+)-PHNO: dissection of D3 signal and anatomy. Neuroimage 54:264–77

    PubMed  CAS  Google Scholar 

  191. Searle G et al (2010) Imaging dopamine D(3) receptors in the human brain with positron emission tomography, [(11)C]PHNO, and a selective D(3) receptor antagonist. Biol Psychiatry 68:392–399

    PubMed  CAS  Google Scholar 

  192. Sokoloff P et al (1992) Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor. Eur J Pharmacol 225(4):331–7

    PubMed  CAS  Google Scholar 

  193. Narendran R et al (2007) Amphetamine-induced dopamine release: duration of action as assessed with the D2/3 receptor agonist radiotracer (-)-N-[(11)C]propyl-norapomorphine ([11 C]NPA) in an anesthetized nonhuman primate. Synapse 61(2):106–9

    PubMed  CAS  Google Scholar 

  194. Green AL, El Haut MJ (1978) Inhibition of mouse brain monoamine oxidase by (+) amphetamine in vivo. J Pharm Pharmacol 30:262–263

    PubMed  CAS  Google Scholar 

  195. Uretsky NJ, Snodgrass SR (1977) Studies on the mechanism of stimulation of dopamine synthesis by amphetamine in striatal slices. J Pharmacol Exp Ther 202:565–580

    PubMed  CAS  Google Scholar 

  196. Grady EF, Bohm SK, Bunnett NW (1997) Turning off the signal: mechanisms that attenuate signaling by G protein-coupled receptors. Am J Physiol 273(3 Pt 1):G586–601

    PubMed  CAS  Google Scholar 

  197. Koenig JA, Edwardson JM (1997) Endocytosis and recycling of G protein-coupled receptors. Trends Pharmacol Sci 18(8):276–87

    PubMed  CAS  Google Scholar 

  198. Feger J, Gil-Falgon S, Lamaze C (1994) Cell receptors: definition, mechanisms and regulation of receptor- mediated endocytosis. Cell Mol Biol (Noisy-le-grand) 40(8):1039–61

    CAS  Google Scholar 

  199. Sternini C et al (1996) Agonist-selective endocytosis of mu opioid receptor by neurons in vivo. Proc Natl Acad Sci USA 93(17):9241–6

    PubMed  CAS  Google Scholar 

  200. Fonseca MI, Button DC, Brown RD (1995) Agonist regulation of alpha 1B-adrenergic receptor subcellular distribution and function. J Biol Chem 270(15):8902–9

    PubMed  CAS  Google Scholar 

  201. Barak LS et al (1997) Internal trafficking and surface mobility of a functionally intact beta2-adrenergic receptor-green fluorescent protein conjugate. Mol Pharmacol 51(2):177–84

    PubMed  CAS  Google Scholar 

  202. Roettger BF et al (1995) Dual pathways of internalization of the cholecystokinin receptor. J Cell Biol 128(6):1029–41

    PubMed  CAS  Google Scholar 

  203. Mantyh PW et al (1995) Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo. Proc Natl Acad Sci USA 92(7):2622–6

    PubMed  CAS  Google Scholar 

  204. Faure MP et al (1995) Somatodendritic internalization and perinuclear targeting of neurotensin in the mammalian brain. J Neurosci 15(6):4140–7

    PubMed  CAS  Google Scholar 

  205. Roth BL et al (1998) 5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function. Pharmacol Ther 79(3):231–57

    PubMed  CAS  Google Scholar 

  206. Maloteaux JM, Hermans E (1994) Agonist-induced muscarinic cholinergic receptor internalization, recycling and degradation in cultured neuronal cells. Cellular mechanisms and role in desensitization. Biochem Pharmacol 47(1):77–88

    PubMed  CAS  Google Scholar 

  207. Grady CL et al (1993) Activation of cerebral blood flow during a visuoperceptual task in patients with Alzheimer-type dementia. Neurobiol Aging 14(1):35–44

    PubMed  CAS  Google Scholar 

  208. Barbier P et al (1997) Pergolide binds tightly to dopamine D2 short receptors and induces receptor sequestration. J Neural Transm 104(8–9):867–74

    PubMed  CAS  Google Scholar 

  209. Itokawa M et al (1996) Sequestration of the short and long isoforms of dopamine D2 receptors expressed in Chinese hamster ovary cells. Mol Pharmacol 49(3):560–6

    PubMed  CAS  Google Scholar 

  210. Ng GY et al (1997) Resistance of the dopamine D2L receptor to desensitization accompanies the up-regulation of receptors on to the surface of Sf9 cells. Endocrinology 138(10):4199–206

    PubMed  CAS  Google Scholar 

  211. Barton AC, Black LE, Sibley DR (1991) Agonist-induced desensitization of D2 dopamine receptors in human Y-79 retinoblastoma cells. Mol Pharmacol 39(5):650–658

    PubMed  CAS  Google Scholar 

  212. Vickery RG, von Zastrow M (1999) Distinct dynamin-dependent and -independent mechanisms target structurally homologous dopamine receptors to different endocytic membranes. J Cell Biol 144(1):31–43

    PubMed  CAS  Google Scholar 

  213. Iwata K et al (1999) Dynamin and rab5 regulate GRK2-dependent internalization of dopamine D2 receptors. Eur J Biochem 263(2):596–602

    PubMed  CAS  Google Scholar 

  214. Ito K et al (1999) Sequestration of dopamine D2 receptors depends on coexpression of G- protein-coupled receptor kinases 2 or 5. Eur J Biochem 260(1):112–9

    PubMed  CAS  Google Scholar 

  215. Ko F et al (2002) Dopamine D2 receptors internalize in their low-affinity state. Neuroreport 13(8):1017–20

    PubMed  CAS  Google Scholar 

  216. Namkung Y, Sibley DR (2004) Protein kinase C mediates phosphorylation, desensitization, and trafficking of the D2 dopamine receptor. J Biol Chem 279(47):49533–41

    PubMed  CAS  Google Scholar 

  217. Paspalas CD, Rakic P, Goldman-Rakic PS (2006) Internalization of D2 dopamine receptors is clathrin-dependent and select to dendro-axonic appositions in primate prefrontal cortex. Eur J Neurosci 24(5):1395–403

    PubMed  Google Scholar 

  218. Goggi JL et al (2007) Agonist-dependent internalization of D2 receptors: imaging quantification by confocal microscopy. Synapse 61(4):231–41

    PubMed  CAS  Google Scholar 

  219. Celver J, Sharma M, Kovoor A (2010) RGS9-2 mediates specific inhibition of agonist-induced internalization of D2-dopamine receptors. J Neurochem 114(3):739–49

    PubMed  CAS  Google Scholar 

  220. Sun W et al (2003) In vivo evidence for dopamine-mediated internalization of D2-receptors after amphetamine: differential findings with [3 H]raclopride versus [3 H]spiperone. Mol Pharmacol 63(2):456–62

    PubMed  CAS  Google Scholar 

  221. Chugani DC, Ackermann RF, Phelps ME (1988) In vivo [3 H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization. J Cereb Blood Flow Metab 8(3):291–303

    PubMed  CAS  Google Scholar 

  222. Guo N et al (2009) Impact of D2 receptor internalization on binding affinity of neuroimaging radiotracers. Neuropsychopharmacology 35(3):806–17

    PubMed  Google Scholar 

  223. Skinbjerg M et al (2010) D2 dopamine receptor internalization prolongs the decrease of radioligand binding after amphetamine: a PET study in a receptor internalization-deficient mouse model. Neuroimage 50(4):1402–7

    PubMed  CAS  Google Scholar 

  224. Skinbjerg M et al (2009) Pharmacological characterization of 2-methoxy-N-propylnorapomorphine’s interactions with D2 and D3 dopamine receptors. Synapse 63(6):462–75

    PubMed  CAS  Google Scholar 

  225. Chou YH et al (1999) A PET study of D1-like dopamine receptor ligand binding during altered endogenous dopamine levels in the primate brain. Psychopharmacology 146:220–227

    PubMed  CAS  Google Scholar 

  226. Dumartin B et al (1998) Internalization of D1 dopamine receptor in striatal neurons in vivo as evidence of activation by dopamine agonists. J Neurosci 18(5):1650–61

    PubMed  CAS  Google Scholar 

  227. Ann X, Lewis DA, Sesack SR (1998) Ultrastructural localization of dopamine D1 or D2 receptor immunoreactivity in structures postsynaptic to tyrosine hydroxyalse-positive terminals in the monkey striataum. Soc Neurosci Abst 24:857

    Google Scholar 

  228. Paterson LM et al (2010) Measuring endogenous 5-HT release by emission tomography: promises and pitfalls. J Cereb Blood Flow Metab 30(10):1682–706

    PubMed  CAS  Google Scholar 

  229. Finnema SJ et al (2010) Fenfluramine-induced serotonin release decreases [11 C]AZ10419369 binding to 5-HT1B-receptors in the primate brain. Synapse 64(7):573–7

    PubMed  CAS  Google Scholar 

  230. Ridler K et al (2011) Characterization of in vivo pharmacological properties and sensitivity to endogenous serotonin of [(11) C] P943: a positron emission tomography study in Papio anubis. Synapse 65:1119–27

    PubMed  CAS  Google Scholar 

  231. Cosgrove KP et al (2011) Assessing the sensitivity of [(11) C]p943, a novel 5-HT(IB) radioligand, to endogenous serotonin release. Synapse 65:1113–7

    PubMed  CAS  Google Scholar 

  232. Love TM, Stohler CS, Zubieta JK (2009) Positron emission tomography measures of endogenous opioid neurotransmission and impulsiveness traits in humans. Arch Gen Psychiatry 66(10):1124–34

    PubMed  CAS  Google Scholar 

  233. Zubieta JK et al (2001) Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 293(5528):311–5

    PubMed  CAS  Google Scholar 

  234. Zubieta JK et al (2003) COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 299(5610):1240–3

    PubMed  CAS  Google Scholar 

  235. Ding YS et al (1998) Dopamine D2 receptor mediated regulation of central cholinergic activity: PET studies with [18 F]fluoroepibatidine. J Nucl Med 39:12P

    Google Scholar 

  236. Skaddan MB et al (2001) Acetylcholinesterase inhibition increases in vivo N-(2-[18 F]fluoroethyl)-4-piperidyl benzilate binding to muscarinic acetylcholine receptors. J Cereb Blood Flow Metab 21(2):144–8

    PubMed  CAS  Google Scholar 

  237. Skaddan MB et al (2002) (R)-N-[11 C]methyl-3-pyrrolidyl benzilate, a high-affinity reversible radioligand for PET studies of the muscarinic acetylcholine receptor. Synapse 45(1):31–7

    PubMed  CAS  Google Scholar 

  238. Ma B et al (2004) Sensitivity of [11 C]N-methylpyrrolidinyl benzilate ([11 C]NMPYB) to endogenous acetylcholine: PET imaging vs tissue sampling methods. Nucl Med Biol 31(4):393–7

    PubMed  CAS  Google Scholar 

  239. Kilbourn MR et al (2007) Anesthesia increases in vivo N-([18 F]fluoroethyl)piperidinyl benzilate binding to the muscarinic cholinergic receptor. Nucl Med Biol 34(5):479–82

    PubMed  CAS  Google Scholar 

  240. Frankle WG et al (2009) Tiagabine increases [11 C]flumazenil binding in cortical brain regions in healthy control subjects. Neuropsychopharmacology 34(3):624–33

    PubMed  CAS  Google Scholar 

  241. Miyake N et al (2011) Imaging changes in glutamate transmission in vivo with the metabotropic glutamate receptor 5 tracer [11 C] ABP688 and N-acetylcysteine challenge. Biol Psychiatry 69(9):822–4

    PubMed  CAS  Google Scholar 

  242. Narendran R et al (2011) Evaluation of dopamine D(2/3) specific binding in the cerebellum for the positron emission tomography radiotracer [(11) C]FLB 457: implications for measuring cortical dopamine release. Synapse 65:991–7

    PubMed  CAS  Google Scholar 

  243. Xiao MF et al (2009) Neural cell adhesion molecule modulates dopaminergic signaling and behavior by regulating dopamine D2 receptor internalization. J Neurosci 29(47):14752–63

    PubMed  CAS  Google Scholar 

  244. Souza BR et al (2008) DARPP-32 and NCS-1 expression is not altered in brains of rats treated with typical or atypical antipsychotics. Neurochem Res 33(3):533–8

    PubMed  CAS  Google Scholar 

  245. Iizuka Y et al (2007) Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization. J Neurosci 27(45):12390–5

    PubMed  CAS  Google Scholar 

  246. Kung HF et al (1988) Dopamine D-2 receptor imaging radiopharmaceuticals: Synthesis, radiolabeling, and in vitro binding of R-(+)- and S-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide. J Med Chem 31:1039–1043

    PubMed  CAS  Google Scholar 

  247. Slifstein M et al (2004) In vivo affinity of [18 F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates. Psychopharmacology (Berl) 175(3):274–86

    CAS  Google Scholar 

  248. Halldin C et al (1995) Carbon-11-FLB 457: a radioligand for extrastriatal D2 dopamine receptors. J Nucl Med 36(7):1275–81

    PubMed  CAS  Google Scholar 

  249. Seeman P et al (1985) Dopamine D2 receptor binding sites for agonists. A tetrahedral model. Mol Pharmacol 28(5):391–9

    PubMed  CAS  Google Scholar 

  250. Seeman P et al (2005) Antiparkinson concentrations of pramipexole and PHNO occupy dopamine D2(high) and D3(high) receptors. Synapse 58(2):122–8

    PubMed  CAS  Google Scholar 

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Acknowledgments

The author would like to acknowledge the multiple investigators with who he had the privilege to collaborate on the questions discussed in this chapter over the years, including but not limited to, Robert B. Innis at Yale University, New Haven, CT, Anissa Abi-Dargham, Mark Slifstein, Lawrence S. Kegeles, Diana Martinez, and Raj Narendran at Columbia University, New York, NY and Eugeni A. Rabiner and Roger M. Gunn at GlaxoSmithKline, London, UK.

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  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Marc Laruelle

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  1. , Dept. of Psychiatry, Psychotherapy,, RWTH Aachen University, Pauwelsstr. 30, Aachen, 52074, Germany

    Gerhard Gründer

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Laruelle, M. (2012). Measuring Dopamine Synaptic Transmission with Molecular Imaging and Pharmacological Challenges: The State of the Art. In: Gründer, G. (eds) Molecular Imaging in the Clinical Neurosciences. Neuromethods, vol 71. Humana Press, Totowa, NJ. https://doi.org/10.1007/7657_2012_45

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