Skip to main content
Log in

Striatal binding of11C-NMSP studied with positron emission tomography in patients with persistent tardive dyskinesia: no evidence for altered dopamine D2 receptor binding

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

Dopamine D2 receptor binding characteristics were studied by positron emission tomography (PET) using N-11C-methyl spiperone as receptor ligand in patients on longterm treatment with neuroleptic drugs and in control subjects. Eight of the patients had symptoms of tardive dyskinesia whereas three patients did not have any symptoms. Control subjects comprised 5 healthy volunteers and 7 patients with pituitary tumors. All patients had been free of neuroleptic drugs for at least 4 weeks. The time dependent regional radioactivity in the striatum was measured and the receptor binding rate, k3, proportional to receptor number, Bmax and association rate for the receptor was calculated in relation to the cerebellum. The lack in difference in k3 values between TD patients, neuroleptic treated patients without TD and control subjects throws doubt on the hypothesis that changes in striatal D2 dopamin receptor number or binding affinity is an etiological mechanism for persistent TD.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andersson U, Häggström J-E, Levin ED, Bondesson U, Valverius M, Gunne LM (1989) Reduced glutamate decarboxylase activity in the subthalamic nucleus in patients with tardive dyskinesia. Movement Disord 44: 37–46

    Google Scholar 

  • Arnett CD, Shine C-Y, Wolf AP, Fowler JS, Logan J, Watanabe M (1985) Comparison of three18F-labelled butyrophenone neuroleptic drugs in the baboon using positron emission tomography. J Neurochem 44: 835–844

    Google Scholar 

  • Asper H, Baggiolini M, Burki HR, Lauener H, Ruch W, Stille G (1973) Tolerance phenomena with neuroleptics. Catalepsy, apomorphine stereotypies and striatal dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol. Eur J Pharmacol 22: 287–294

    Google Scholar 

  • Bergström M, Boethius J, Eriksson L, Greitz T, Ribbe T, Widén L (1981) Head fixation device for reproducible positron emission tomography. J Comput Assist Tomogr 5: 136–141

    Google Scholar 

  • Burt DR, Creese J, Snyder SH (1977) Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 196: 326–327

    Google Scholar 

  • Casey DE, Gerlach J (1986) Is tardive dyskinesia due to dopamine hypersensitivity? Clin Neuropharmacol 9: 134–136

    Google Scholar 

  • Christensen AV, Fjalland B, Møller Nielsen I (1976) On the hypersensitivity of dopamine receptors, induced by neuroleptics. Psychopharmacology 48: 1–6

    Google Scholar 

  • Clow A, Jenner P, Marsden CD (1978) An experimental model of tardive dyskinesias. Life Sci 23: 421–424

    Google Scholar 

  • Clow A, Jenner P, Theodorou A, Marsden CD (1979 a) Striatal dopamine receptors become supersensitive while rats are given trifluoperazine for six months. Nature 278: 59–61

    Google Scholar 

  • Clow A, Jenner P, Marsden CD (1979 b) Changes in dopamine mediated behaviour during one years's neuroleptic administration. Eur J Pharmacol 57: 365–375

    Google Scholar 

  • Crane GE, Naranjo ER (1971) Motor disorders induced by neuroleptics. A proposed new classification. Arch Gen Psychiatry 24: 179–184

    Google Scholar 

  • Cross AJ, Crow TJ, Ferrier IN, Johnson JA, Johnstone EC, Owen F, Owens DGC, Poulter M (1985) Chemical and structural changes in the brain in patients with movement disorder. In: Casey DE, Chase TN, Christensen AV, Gerlach J (eds) Dyskinesia. Research and treatment. Springer, Berlin Heidelberg New York Tokyo (Psychopharmacol [Suppl 2]: 104–110)

    Google Scholar 

  • Crow TJ, Cross AJ, Johnstone EC, Owen F, Owens DGC, Waddington JL (1982) Abnormal involuntary movements in schizophrenia: are they related to the disease process or its treatment? Are they associated with changes in dopamine receptors? J Clin Psychopharmacol 5: 336–340

    Google Scholar 

  • Crow TJ, Owens DGC, Johnstone EC, Cross AJ, Owen F (1983) Does tardive dyskinesia exist? Mod Probl Pharmacopsychiatry 21: 206–219

    Google Scholar 

  • Dannais RF, Burns D, Ravert H, Långström B, Duelfer T, Wilson A, Zeyman S, Wagner H (1984) Radiosynthesis of a dopamine receptor-binding radiotracer for positron emission tomography:11C-methyl-3-N-methyl spiperone. J Label Compound Radiopharm 21: 1146–1151

    Google Scholar 

  • Degkwitz R, Wenzel W, Binsack KF, Herkert H, Luxenberger O (1966) Zum Problem der terminalen extrapyramidalen Hyperkinesen an Hand von 1600 langfristig mit Neuroleptica Behandelten. Arzneim Forsch 16: 276–279

    Google Scholar 

  • DeLong MR, Georgopoulos AP (1979) Physiology of the basal ganglia—a brief overview. In: Chase TN et al (eds) Advances in Neurology. Raven Press, New York, pp 137–153

    Google Scholar 

  • Eckernäs S-Å, Aquilonius S-M, Hartvig P, Hägglund J, Lundkvist H, L↭gström B (1987) Positron emission tomography (PET) in the study of dopamine receptors in the primate brain: evaluation of a kinetic model using11C-N-methyl-spiperone. Acta Neurol Scand 75: 168–178

    Google Scholar 

  • Farde L, Wiesel F-A, Hall H, Halldin H, Stone-Elander S, Sedvall G (1987) No D2 receptor increase in PET study of schizophrenia. Arch Gen Psychiatry 44: 671–672

    Google Scholar 

  • Fibiger HC, Lloyd KG (1984) Neurobiological substrates of tardive dyskinesia: the GAB A hypothesis. TINS 7: 462–464

    Google Scholar 

  • Frost JJ, Smith AC, Kuhar MJ, Dannals RF, Wagner Jr HN (1987) In vivo binding of3H-N-methyl-spiperone to dopamine and serotonin receptors. Life Sci 40: 987–995

    Google Scholar 

  • Gerlach J, Reisby N, Randrup A (1974) Dopamine hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia 34: 21–35

    Google Scholar 

  • Gianutsos G, Moore KE (1977) Dopaminergic supersensitivity in striatum and olfactory tubercle following chronic administration of haloperidol or clozapine. Life Sci 20: 1585–1592

    Google Scholar 

  • Gjedde A (1982) Calculation of glucose phosphorylation from brain uptake of glucose analogs in vivo: a re-examination. Brain Res Rev 4: 237–274

    Google Scholar 

  • Gunne LM, Häggström J-E (1984) Reduction of nigral glutamic acid decarboxylase in rats with neuroleptic-induced oral dyskinesia. Psychopharmacology 81: 191–194

    Google Scholar 

  • Gunne LM, Häggström J-E, Sjöquist B (1984) Association with persistent neurolepticinduced dyskinesia of regional changes in brain GABA synthesis. Nature 309: 347–349

    Google Scholar 

  • Gunne LM, Bachus SE, Gale K (1988) Oral movements induced by interference with nigral GABA neurotransmission: relationship to tardive dyskinesia. Exp Neurol 100: 459–469

    Google Scholar 

  • Guy W (ed) ECDEU Assessment manual for psychopharmacology. U.S. Department of Health, Education and Welfare publication, No. 76-338, Washington, DC, US. 1976, Government printing office

    Google Scholar 

  • Hyttel J, Larsen J-J, Chistensen AV, Arnt J (1985) Receptor-binding profiles of neuroleptics. In: Casey DE, Chase TN, Christensen AV, Gerlach J (eds) Dyskinesia. Research and treatment. Springer, Berlin Heidelberg New York Tokyo (Psychopharmacol [Suppl 2]: 9–18)

    Google Scholar 

  • Jeste DV, Wyatt RJ (1982) Understanding and treating tardive dyskinesia. Guilford Press, New York, pp 136–137

    Google Scholar 

  • Klawans HL (1973) The pharmacology of tardive dyskinesia. Am J Psychiatry 130: 82–86

    Google Scholar 

  • Klawans HL, McKendall R (1971) Observations on the effect of levodopa on tardive lingual-facial-buccal dyskinesia. J Neurol Sci 14: 189–192

    Google Scholar 

  • Kuhar MJ, Murrin CL, Malouf AT, Klemm N (1978) Dopamine receptor binding in vivo: the feasibility of autoradiographic studies. Life Sci 22: 203–210

    Google Scholar 

  • Künzle H (1976) Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia: an autoradiographic study in macaca fascicularis. Brain Res 88: 195–209

    Google Scholar 

  • Långström B, Antoni G, Gullberg P, Halldin C, Malmborg P, Någren K, Rimland A, Svärd H (1987) Synthesis of L- and D-methyl-11C methionine. J Nucl Med 37: 1037–1040

    Google Scholar 

  • Martres M-P, Bouthenet M-L, Sales N, Sokoloff P, Schwartz J-C (1985) Widespread distribution of brain dopamine receptors evidenced with [125I] Iodosulpride, a highly selective ligand. Science 228: 752–755

    Google Scholar 

  • Møller Nielsen I, Fjalland B, Pederson V, Nymark M (1974) Pharmacology of neuroleptics upon repeated administration. Psychopharmacologia 34: 95–104

    Google Scholar 

  • Morgan DG, Marcusson JO, Finch CE (1984) Contamination of serotonin-2 binding sites by an alpha-1 adrenergic component in assays with (3H) spiperone. Life Sci 34: 2507–2514

    Google Scholar 

  • Muhr C, Bergström M, Lundberg P-O, Bergström K, Hartvig P, Lundquist H, Antoni G, Längström B (1986) Dopamine receptors in pituitary adenomas: PET visualization with11C-N-Metylspiperone. J Comput Assist Tomogr 2: 175–180

    Google Scholar 

  • Owen F, Cross AJ, Waddington JL, Poulter M, Gamble SJ, Crow TJ (1980) Dopamine-mediated behaviour and3H-spiperone binding to striatal membranes in rats after nine months haloperidol administration. Life Sci 26: 55–59

    Google Scholar 

  • Ögren SO, Hall H, Köhler C, Magnusson O, Sjöstrand S-E (1986) The selective dopamine D2 receptor antagonist raclopride discriminates between dopamine-mediated motor functions. Psychopharmacology 90: 287–294

    Google Scholar 

  • Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3: 1–7

    Google Scholar 

  • Patlak CS, Blasberg RG (1985) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab 5: 584–590

    Google Scholar 

  • Ruberg M, Bokoza B, Javoy-Agid F, Montfort J-C, Agid Y (1984) (3H) Spiperone binding in the nigrostriatal system in human brain. Eur J Pharmacol 99: 159–165

    Google Scholar 

  • Schooler NR, Kane JM (1982) Research diagnosis for tardive dyskinesia. Arch Gen Psychiatry 39: 486–487

    Google Scholar 

  • Sedvall G, Farde L, Persson A, Wiesel F-A (1986) Imaging of neurotransmitter receptors in the living human brain. Arch Gen Psychiatry 43: 995–1005

    Google Scholar 

  • Tarsy D, Baldessarini RJ (1973) Pharmacologically induced behavioral supersensitivity to apomorphine. Nature (New Biol) 245: 262–263

    Google Scholar 

  • Tarsy D, Baidessarini RJ (1974) Behavioral supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines. Neuropharmacology 13: 927–940

    Google Scholar 

  • Waddington JL (1986) Further anomalies in the dopamine receptor supersensitivity hypothesis of tardive dyskinesia. TINS 8: 200

    Google Scholar 

  • Wong DF, Wagner Jr HN, Dannals RF, Links JM, Frost JJ, Ravert HT, Wilson AA, Rosenbaum AE, Gjedde A, Douglass KH, Petronis JD, Folstein MF, Toung JKT, Burns HD, Kuhar MJ (1984) Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science 226: 1393–1396

    Google Scholar 

  • Wong DF, Wagner HN, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Brousolle EP, Ravert HT, Wilson AA, Young TK, Malat J, Williams JA, O'Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234: 1558–1563

    Google Scholar 

  • Wong DF, Gjedde A, Wagner HN, Dannals RF, Links JM, Tune LE, Pearlson GD (1988) Elevated D2 dopamine receptors in drug-naive schizophrenics. Response. Science 239: 790–791

    Google Scholar 

  • Zeeberg BR, Gibson RE, Reba RC (1988) Elevated D2 dopamine receptors in drug-naive schizophrenics. Science 239: 789–790

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andersson, U., Eckernäs, S.Å., Hartvig, P. et al. Striatal binding of11C-NMSP studied with positron emission tomography in patients with persistent tardive dyskinesia: no evidence for altered dopamine D2 receptor binding. J. Neural Transmission 79, 215–226 (1990). https://doi.org/10.1007/BF01245132

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01245132

Keywords

Navigation