A Critical Analysis of Neurochemical Methods for Monitoring Transmitter Dynamics in the Brain

Janet M. Finlay1 and Gwenn S. Smith2
Departments of Neuroscience1 and Radiology2
University of Pittsburgh and University of Pittsburgh Medical Center

Janet M. Finlay
Department of Neuroscience
University of Pittsburgh
570 Crawford Hall
Pittsburgh, PA 15260
(412) 624-8581 (phone)
(412) 624-9198 (fax)


  1. Adams RN. Probing brain chemistry with electroanalytical techniques. Anal Chem 1976;48:1128A-1138A.

  2. Benveniste H, Hansen AJ. Practical aspects of using microdialysis for determination of brain interstitial concentrations. In: Robinson TE and Justice, JB, Jr. Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences. New York: Elsevier Science Publisher, 1991;7:81-96.

  3. Benveniste H, Hüttemeier PC. Microdialysis - Theory and application. Prog Neurobiol 1990;35:195-215.

  4. Benvineste H, Hansen AJ, Ottosen NS. Determination of brain interstitial concentrations by microdialysis. J Neurochem 1990;52:1741-1750.

  5. Benvineste H. Brain microdialysis. J Neurochem 1989;52:1667-1679.

  6. Bergson C, Mrzljak L, Smiley JF, Pappy M, Levenson R, Goldman-Rakic PS. Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain. J Neuroscience 1995;15:7821-7836.

  7. Bhattacharya BK, Fedlberg W. Perfusion of cerebral ventricles: Assay of pharmacologically active substances in the effluent from the cisterna and the aqueduct. Br J Pharmacol 1958b;13:163-174.

  8. Bhattacharya BK, Feldberg W. Perfusion of cerebral ventricles: Effects of drugs on outflow from the cisterna and the aqueduct. Br J Pharmacol 1958a;13:156-162.

  9. Bito R, Davson H, Levin EM, Murray M, Snider N. The concentration of free amino acids and other electrolytes in cerebrospinal fluid, in vivo dialysate of brain and blood plasma of the dog. J Neurochem 1966;13:1057-1067.

  10. Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, Eckelman WC, Pickar D. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci USA 1997;94(6):2569-2574.

  11. Brodie BB, Costa E, Dlabac A, Neff NH, Smookler HH. Application of steady-state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines. J Pharmacol Exp Ther 1966;154:493-498.

  12. Brownstein MJ. Neuropeptides. In: Siegel GJ, Agranoff BW, Albers RW, Molinoff PB, eds. Basic Neurochemistry, 5th ed. New York: Raven Press, 1994;341-365.

  13. Bungay RL, Morrison PF, Dedrick RL. Steady-state theory for quantitative microdialysis application to in vivo sampling of tritiated water. Life Sci 1990;46:105-119.

  14. Cadoni C, Pinna A, Russi G, Consolo S, and DiChiara G. Role of vesicular dopamine in the in vivo stimulation of striatal dopamine transmission by amphetamine: evidence from microdialysis and Fos immunohistochemistry. Neuroscience 1995;65:1027-1039.

  15. Carlsson A, Davis JN, Kehr W, Lindqvist M, Atack CV. Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn Schmeidbergs Arch Pharmacol 1972;275:153-168.

  16. Chaudhuri A. Neural activity mapping with inducible transcription factors. Neuroreport 1997;8:iii-vii.

  17. Chen G and Ewing AG. Chemical analysis of single cells and exocytosis. Crit Rev Neurobiol 1997;11:59-90.

  18. Costa E, Neff NH. Estimation of turnover rates to study the metabolic regulation of the steady-state level of neuronal monoamines. In: Lajtha A, ed. Handbook of Neurochemistry, vol. 4. New York: Plenum Press, 1970;45-90.

  19. Damsma G, Westerink HC. A microdialysis and automated on-line analysis approach to study central cholinergic transmission in vivo. In: Robinson TE and Justice JB, Jr., eds. Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences. New York: Elsevier Science Publishers, 1991;7:237-249.

  20. DeBoer P. and Abercrombie ED. Physiological release of striatal acetylcholine in vivo: modulation by D1 and D2 dopamine receptor subtypes. J Pharmacol Exp Ther 1996;277:775-783.

  21. Delgado JMR. Pharmacological modifications of social behavior. In: Paton WDM, ed. Pharmacological Analysis of Central Nervous Action. Oxford:Pergamon Press, 1962;265-292.

  22. Delgado JMR. Telecommunication in brain research. In: Schwabe, Basel. Proc IV International Congress of Pharmacology. 1970;5:270-278.

  23. Delgado JMR, De Feudis FV, Roth RH, Ryugo DK, Mitruka BM. Dialytrode for long term intracerebral perfusion in awake monkeys. Arch Int Pharmacodyn 1972;198:9-21.

  24. Dewey S, Smith G, Logan J, Brodie J, Yu D, Ferrieri R, King P, MacGregor R, Martin T, Wolf A, Volkow N, Fowler J. GABAergic inhibition of endogenous dopamine release measured in vivo with [11C]-raclopride and positron emission tomography. J Neurosci 1992;12:3773-3780.

  25. Dewey SL, Smith GS, Logan J, Brodie JD, Fowler JS, Wolf AP. Striatal binding of the PET ligand 11C-raclopride is altered by drugs that modify synaptic dopamine levels. Synapse 1993;13: 350-356.

  26. Dewey SL, Smith G, Logan J, Simkowitz P, Brodie JD, Fowler JS, Volkow N, Wolf AP Effects of central cholinergic blockade on striatal dopamine release measured with positron emission tomography (PET) in normal human subjects. Proc Nat Acad Sci 1993;90:11816-11820.

  27. Egawa M, Hoebel BG, Stone EA. Use of microdialysis to measure brain noradrenergic receptor function in vivo. Brain Res 1988;458:303-308.

  28. Fox RH, Hilton SM. Bradykinin formation in human skin as a factor in heat vasodilation. J Physiol (London) 1953;142:219-232.

  29. Fuxe K, Agnati LF, eds. Advances in Neuroscience, Volume 1: Transmission in the Brain: Novel Mechanisms for Neural Transmission. New York: Raven Press, 1991.

  30. Gaddum JH. Push-pull cannulae. J Physiol (London) 1961;155:1P.

  31. Gaddum JH. Substances released in nervous activity. In: Paton WD, Lindgren P eds. Pharmacological Analysis of Central Nervous Action. London: Permagon Press, 1962;1-6.

  32. Gardner EL, Chen J, Paredes W. Overview of chemical sampling techniques. J Neursci Meth 1993;48:173-197.

  33. Garris PA, Wightman RM. Different kinetics govern dopaminergic transmission in the amygdala, prefrontal cortex, and striatum: an in vivo voltammetric study. J Neurosci 1994;14:442-450.

  34. Gerhardt GA, Oke AF, Nagy G, Moghaddam B, Adams RN. Nafion-coated electrodes with high selectivity of CNS electrochemistry. Brain Res 1984;290:390-395.

  35. Glowinski J, Iversen LL. Regional studies of catecholamines in the rat brain: the disposition of 3H-norepinephrine, 3H-dopamine, 3H-dopa in various regions of the brain. J Neurochem 1966;13:665-669.

  36. Hamani C, Luer MS, Dujovny M. Microdialysis in the human brain: review of its applications. Neurol Res 1997;19:281-288.

  37. Herrera DG, Robertson HA. Activation of c-fos in the brain. Prog Neurobiol 1996;50:83-107.

  38. Hillered L, Persson L. Microdialysis for metabolic monitoring in cerebral ischemia and trauma: Experimental and clinical studies. In: Robinson TE, Justice JB, Jr. eds. Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences New York: Elsevier Science Publishers, 1991;7:389-403.

  39. Humpel C, Ebendal T, Olson L. Microdialysis: a way to study in vivo release of neurotrophic bioactivity: a critical summary. J Mol Med 1996;74:523-526.

  40. Jacobson I, Sandbergh M, Hamberger A. Mass transfer in brain dialysis devices - A new method for the estimation of extracellular amino acid concentration. J Neurosci Methods 1985;15:263-268.

  41. Justice JB, Jr. Quantitative microdialysis of neurotransmitters. J Neurosci Methods 1993;48:263-276.

  42. Kawagoe KT, Zimmerman JB, Wightman RM. Principles of voltammetry and microelectrode surface states. J Neurosci Methods 1993;48:225-240.

  43. Kehr J. A survey on quantitative microdialysis: theoretical models and practical implications. J Neurosci 1993; 48:251-261

  44. Kissinger PT. Electrochemical detection in bioanalysis. J Pharm Biomed Anal 1996;14:871-880.

  45. Kissinger PT, Hart JB, Adams RN. Voltammetry in brain tissue - a new neurophysiological measurement. Brain Res 1973;55:209-213.

  46. Kissinger PT, Refshuage CJ, Dreiling R, Blank L, Freeman R, Adams RN An electrochemical detector for liquid chromatography with picogram sensitivity. Anal Lett 1973;6:465-477

  47. Korf J, Grasdijk L, Westerink BHC. Effects of electrical stimulation of the nigrostriatal pathway of the rat on dopamine metabolism. J Neurochem 1976;26:579-584.

  48. Lehmann A, Sandberg M, Huxtable RJ. In vivo release of neuroactive amines and amino acids from the hippocampus of seizure-resistant and seizure-susceptible rats. Neurochem Int 1986;8:513-520.

  49. Lipton P. Brain slices: uses and abuses. In: Boulton AA, Baker GB, eds. Neuromethods, Series I: Neurochemistry, vol 1, General Neurochemical Techniques. Clifton, NJ:Humana Press, 1985.

  50. Lonnroth P, Jannson P-A, Smith U. A microdialysis method allowing characterization of intercellular water space in humans. Am J Physiol 1987;253:E228-E231.

  51. MacIntosh FC, Oborin PE. Release of acetylcholine from intact cerebral cortex. Abstr XIX Int Physiol Congr, 1953; 580-581.

  52. Maidment NT, Evans CJ. Measurement of extracellular neuropeptides in the brain: microdialysis linked to solid-phase radioimmunoassays with sub-femtomole limits of detection. In: Robinson TE, Justice JB, Jr. Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences. Vol 7. New York: Elsevier Science Publishers, 1991;275-301.

  53. Marsden CA, ed. Measurement of Neurotransmitter Release In Vivo. New York: John Wiley & Sons Ltd, 1984;127-148.

  54. Marsden CA, Braxell MP, Maidment NT. An Introduction to In Vivo Electrochemistry. In: Marsden CA, ed. Measurement of Neurotransmitter Release In Vivo. New York: John Wiley & Sons Ltd, 1984;127-148.

  55. Marsden CA, Joseph MH, Kruk ZL, Maidment NT, O'Neill RD, Schenk JO, Stamford JA. In vivo voltammetry - Present electrodes and methods. Neurosci 1988;25(2):389-400.

  56. Moghaddam B, Bunney BS. Ionic composition of microdialysis perfusing solution alters the pharmacological responsiveness and basal outflow of striatal dopamine. J Neurochem 1989;53:652-654.

  57. Moroni F, Pepeu G. The cortical cup technique. In: Marsden CA, ed. Measurement of Neurotransmitter Release In Vivo. IBRO Handbook Series: Methods in the Neurosciences, Vol 6.New York: John Wiley & Sons Ltd, 1984;63-76.

  58. Mrzljak L, Berson C, Pappy M, Huff R, Leveson R, Goldman-Rakic PS. Localization of dopamine D4 receptors in GABAergic neurons of the primate brain. Nature 1996;381:245-248.

  59. Myers RD. Development of push-pull systems for perfusion of anatomically distinct regions of the brain of the awake animal. Ann NY Acad Sci 1986;473:21-41.

  60. Myers RD, Adell A, Lankford MF. Simultaneous comparison of cerebral dialysis and push-pull perfusion in the brain of rats: a critical review. Neurosci Biobehav Rev 1998; 22:371-387.

  61. Neff NM, Tozer TN. In vivo measurement of brain serotonin turnover. Adv Pharmacol 1968;6a:97-109.

  62. Nieoullon A, Cheramy A, Glowinski J. Release of dopamine in vivo from cat substantia nigra. Nature 1977;266:375-377.

  63. Osborne PG, O'Connor WT, Ungerstedt U. Effect of varying the ionic concentration of a microdialysis perfusate on basal striatal dopamine levels in awake rats. J Neurochem 1990;56:452-456.

  64. Robertson GS, Vincent SR, Fibiger HC. D1 and D2 dopamine receptors differentially regulate c-fos expression in striatonigral and striatopallidal neurons. Neuroscience 1992;49:285-296.

  65. Robinson TE, Camp DM. The feasibility of repeated microdialysis for within-subjects design experiments: studies on the mesostriatal dopamine system. In: Robinson TE, Justice JB, Jr., eds. Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences. Vol 7. New York: Elsevier Science Publishers, 1991;189-218.

  66. Robinson TE, Justice JB, Jr., eds. Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences. New York: Elsevier Science Publisher, 1991;7:81-96.

  67. Rueter LE, Fornal CA, Jacobs BL. A critical review of 5-HT brain microdialysis and behavior. Rev Neurosci 1997;8:117-137.

  68. Sesack S, Bressler C, Lewis D. Ultrastructural associations between dopamine terminals and local circuit neurons in the monkey prefrontal cortex: a study of calretinin-immunoreactive cells. Neuroscience Letters 1995;200:9-12.

  69. Sesack S, Hawrylak V, Matus C, Guido M, Levey A. Dopamine axon varicosities in the prelimbic division of the rat prefrontal cortex exhibit sparse immunoreactivity for the dopamine transporter. J Neurosci 1998;18:2697-2708.

  70. Sharp T, Zetterstrom T, Ungerstedt U. An in vivo study of dopamine release and metabolism in rat brain regions using intracerebral dialysis. J Neurochem 1986;47:113-122.

  71. Sherman KA, Hanin I, Zigmond MJ. The effect of neuroleptics on acetylcholine concentration and choline uptake in striatum: implications for regulation of acetylcholine metabolism. J Pharmacol Exp Ther 1978;621: 677-686.

  72. Simon JR, Atweh S, Kuhar MJ. Sodium-dependent high affinity choline uptake: a regulatory step in the synthesis of acetylcholine. J Neurochem 1976;26: 909-922.

  73. Smith G, Dewey SL, Logan J, Brodie JD, Vitkun S, Simkowitz P, Alexoff D, Volkow N. The serotonin-dopamine interaction measured with positron emission tomography (PET) and [11C]-raclopride in normal human subjects. Am J Psychiatry 1997; :490-496.

  74. Smith G, Price J, Lopresti B, Huang Y, Simpson N, Holt D, Mason NS, Sweet R, Meltzer CC, Nichols T, Sashin D, Mathis C. Test-retest variability of positron emission tomography (PET) and [18F]-altanserin for the in vivo imaging of serotonin (5-HT2A) receptors in the human brain. Synapse 1998;30:380-392.

  75. Stamford JA, ed. Monitoring neuronal activity: a practical approach. Oxford: IRL Press, 1992.

  76. Stone EA, Zhang Y, John SM, Bing G. C-Fos response to administration of catecholamines into brain by microdialysis. Neurosci Lett 1991;133:33-35.

  77. Timmerman W, Westerink BH. Brain microdialysis of GABA and glutamate: what does it signify? Synapse 1997;27:242-261.

  78. Ungerstedt U. Introduction to intracerebral microdialysis. In: Robinson TE, Justice JB, Jr., eds. Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences. Vol 7. New York: Elsevier Science Publishers, 1991; 3-18.

  79. Ungerstedt U. Measurement of neurotransmitter release by intracranial dialysis. In: Marsden CA, ed. Measurement of Neurotransmitter Release In Vivo. IBRO Handbook Series: Methods in the Neurosciences, Vol 6. New York: John Wiley & Sons Ltd, 1984; 81-105.

  80. Ungerstedt U, Pycock C. Functional correlates of dopamine neurotransmission. Bull Schweiz Akad Med Wiss 1974;30:44-55.

  81. Ungerstedt U, Herrera-Marshcitz M, Jungnelius U, Ståhle L, Tossman U, Zetterstöm T. Dopamine synaptic mechanisms reflected in studies combining behavioral recordings and brain dialysis. In: Kotisaka M, Shomori T, Tsukada Y, Woodruff GM. Advances in Dopamine Research. New York: Permagon Press, 1982;219-231.

  82. Volkow ND, Wang GJ, Fowler JS, Logan J, Schlyer D, Hitzemann R, Lieberman J, Angrist B, Pappas N, MacGregor R. Imaging endogenous dopamine competition with [11C]-raclopride in the human brain. Synapse 1994;16:255-262.

  83. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Hitzemann R, Chen AD, Dewey SL, Pappas N. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 1997;386(6627):830-833.

  84. Weiner N. A critical assessment of methods for determination of monoamine synthesis and turnover rate in vivo. In: Usdin E, ed. Neuropsychopharmacology of the monoamines and their regulatory enzymes. New York: Raven Press, 1974:143.

  85. Westerink BHC. Sequence and significance of dopamine metabolism in the rat brain. Neurochem Int 1985;7:221-227.

  86. Westerink BHC, Hofsteede HM, Damsma G, de Vries JB. The significance of extracellular calcium for the release of dopamine, acetylcholine and amino acids in conscious rats, evaluated by brain microdialysis. Naunyn-Schmiedeberg's Arch. Pharmacol. 1988;337:373-37.8

  87. Westerink BHC, De Vries JB. Characterization of the in vivo dopamine release as determined by brain microdialysis after acute and subacute implantations; methodological aspects. J Neurochem 1988;51:683-687.

  88. Westerink BHC, Justice JB. Microdialysis compared with other in vivo release models. In: Robinson TE, Justice JB, Jr., eds. Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences. Vol 7. New York: Elsevier Science Publishers, 1991;23-40.

  89. Wightman RM, Brown DS, Huhr WG, Wilson RL. Molecular specificity of in vivo electrochemical measurements. In Justice JB, ed. Voltammetry in the Neurosciences. 1987;103-108.

  90. Zetterström T, Sharp T, Marsden CA, Ungerstedt U. In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine. J Neurochem 1983;41:1769-1773.

  91. Zilversmit DB. The design and analysis of isotope experiments. Amer J Med 1960;2:832-848.

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published 2000