Summary
The in vivo binding of [3 H]N-methylspiperone (NMSP) and [3 H]raclopride was compared in mice treated with reserpine (5 mg/kg, 24 hr prior to the tracer injection). With both radioligands, selective accumulation of radioactivity in the striatum following intravenous injection was observed, whereas a relatively low accumulation and a rapid decline in radioactivity in the cerebellum was seen. Reserpine significantly decreased [3 H]NMSP binding in vivo, however it increased [3 H]raclopride binding. By compartment model analysis, it was found that the decrease in [3 H]NMSP binding was primarily due to the decrease in the association rate (K3) and the increase in [3 H]raclopride was due to the decrease in the dissociation rate (K4) in vivo. As both Kd and Bmax of dopamine D2 receptors have been reported to be unaltered by reserpine, these results suggested that some unknown factors except Kd and Bmax which influence on in vivo binding of receptors might be changed by reserpine. These results revealed that it is of importance to measure kinetics of ligand-receptor binding in vivo rather than static analysis. These two different types of radioligands can be combined to reveal functional roles of dopamine receptor in vivo, especially in the study of the human brain with positron emission tomography (PET).
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References
Baudary M, Martres MP, Schwartz JC (1977) In vivo binding of [3 H]-pimozide in mouse striatum: effect of dopamine agonists and antagonists. Life Sci 21: 1163–1170
Bischoff S, Bittiger H, Krauss J, Vassout A, Waldmeier P (1984) Affinity changes of rat striatal dopamine receptors in vivo after acute bupropion treatment. Eur J Pharmacol 104: 173–176
Chugani DC, Ackermann RF, Phelps ME (1988) In vivo [3 H]spiperone binding: evidence for accumulation in corpus striatumy agonist-mediated receptor internalization. J Cereb Blood Flow Metab 8: 291–303
Crawley JCW, Crow TJ, Johnstone EC, Oldland SRD, Owen F, Owens DGC, Smith T, Veall N, Zanelli GD (1986) Uptake of77Br-spiperone in the striata of schizophrenic patients and controls. Nucl Med Commun 7: 599–607
Ebersole BJ, Weinstein H, Maayani S (1984) Difference in d-[3 H] lysergic acid diethylamide binding in mouse cortex and hippocampus in vivo and in vitro by radioautography and rapid filtration studies. J Pharmacol Exp Ther 229: 865–871
Farde L, Hall H, Ehrin E, Sedvall G (1986) Quantitative analysis of dopamine-D2 receptor binding in the living human brain by positron emission tomography. Science 231: 258–261
Farde L, Wiesel F-A, Elander SS, Halldin C, Nordstrom AL, Hall H, Sedvall G (1990) D2 dopamine receptors in neuroleptic-naive schizophrenic patients. Arch Gen Psychiatry 47: 213–219
Frost JJ, Douglass KH, Mayberg HS, Dannals RF, Links JM, Wilson AA, Ravert HT, Crozier WC, Wagner HN (1989) Multicompartmental analysis of [11 C]-carfentanil binding to opiate receptors in humans measured by positron emission tomography. J Cereb Blood Flow Metab 9: 398–409
Frost JJ, Smith AC, Kuhar MJ, Dannals RF, Wagner HN (1987) In vivo binding of [3 H]N-methylspiperone to dopamine and serotonin receptors. Life Sci 40: 987–995
Hollt V, Czlonkowski A, Herz A (1977) The demonstration of in vivo specific binding sites for neuroleptic drugs in mouse brain. Brain Res 130: 176–183
Insel TR (1989) Decreased in vivo binding to brain benzodiazepine receptors during social isolation. Psychopharmacology 97: 142–144
Jarvie KR, Nizniik HB, Seeman P (1987) Dopamine D2 receptors in canine brain: ionic effect on [3 H]neuroleptic binding. Eur J Pharmacol 144: 163–171
Kohler C, Karlsson-Boethius G (1988) In vivo labelling of rat brain dopamine D2 receptors, stereoselective blockade by the D2 antagonist raclopride and its enantiomer of [3 H]spiperone, [3 HN]N-propylnorapomorphine and [3 H]raclopride binding in the rat brain. J Neural Transm 73: 87–100
Kuhar MJ, Murrin LC, Malouf AT, Klemm N (1978) Dopamine receptor binding in vivo: the feasibility of autoradiographic studies. Life Sci 22: 203–210
Laduron P, Janssen PFM, Leysen JE (1978) Spiperone: a ligand of choice for neuroleptic receptors. Biochem Pharmacol 27: 317–321
Miller LG, Deutsch SI, Greenblatt DJ, Paul SM, Shader RI (1988) Acute barbiturate administration increases benzodiazepine receptor binding in vivo. Psychopharmacology 96: 385–390
Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ (1984) A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann Neurol 15: 217–227
Perry DC, Mullis KB, Oie S, Sadee W (1980) Opiate antagonist receptor binding in vivo: evidence for a new receptor binding model. Brain Res 199: 49–61
Ross SB, Jackson DM (1989) Kinetic properties of the accumulation of [3 H]raclopride in the mouse brain in vivo. Naunyn Schmiedebergs Arch Pharmacol 340: 6–12
Smith M, Wolf AP, Brodie JD, Arnett CD, Barouche F, Shiue C-Y, Fowler JS, Russell AG, MacGregor RR, Wolkin A, Angrist B, Rotrosen J, Peselow E (1988) Serial [18 F]N-methylspiperone PET studies to measure changes in antipsychotic drug D2 receptor occupancy in schizophrenic patients. Biol Psychiatry 23: 653–663
Theodorou AE, Hall MD, Jenner P, Marsden CD (1980) Cation regulation differentiates specific binding of [3 H]sulpiride and [3 H]spiperone to rat striatal preparation. J Pharm Pharmacol 32: 441–444
Theodorou AE, Jenner P, Marsden CD (1983) Cation specificity of striatal binding involves alteration in the number of striatal binding sites. Life Sci 32: 1243–1254
Van Der Welf JF, Sebens JB, Vaalburg W, Korf J (1983) In vivo binding of N-n-propylnorapomorphine in the rat brain: regional localization, quantification in striatum and lack of correlation with dopamine metabolism. Eur J Pharmacol 87: 259–270
Wagner HN, Burns HD, Dannals RF, Wong DF, Langstrom B, Duelfer T, Frost JJ, Raert HT, Links JM, Rosenblom SB, Lukas SE, Kramer AV, Kuhar MJ (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221: 1264–1266
Weizman R, Weizman A, Kook KA, Vocci F, Deutsch SI, Paul SM (1989) Repeated swim stress alters brain benzodiazepine receptors measured in vivo. J Pharmacol Exp Ther 249: 701–707
Wong DF, Wagner HN, Dannals RF, Links JM, Frost J, Ravert HT, Wilson AA, Rosenbaum AE, Gjedde A, Douglass KH, Petronis JD, Folstein MF, Toung JKT, Burns D, Kuhar MJ (1984) Effect of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science 226: 1393–1396
Wong DF, Wagner HN, Tune LE, Dannals RF, Pearlson EP, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung T, Malat J, Williams JA, O'Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptor in drug-naive schizophrenics. Science 234: 1558–1563
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Inoue, O., Kobayashi, K., Tsukada, H. et al. Difference in in vivo receptor binding between [3 H]N-methylspiperone and [3 H]raclopride in reserpine-treated mouse brain. J. Neural Transmission 85, 1–10 (1991). https://doi.org/10.1007/BF01244652
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DOI: https://doi.org/10.1007/BF01244652