Hostname: page-component-68945f75b7-9klrw Total loading time: 0 Render date: 2024-08-06T01:12:42.721Z Has data issue: false hasContentIssue false
  • English
  • Français

Implications of Positron Emission Tomography Research for the Investigation of the Actions of Antipsychotic Drugs

Published online by Cambridge University Press:  06 August 2018

Stephen J. List  and
John M. Cleghorn
Stephen J. List*
Affiliation:
McMaster University
John M. Cleghorn
Affiliation:
Clarke Institute of Psychiatry, Toronto, and Professor Emeritus of Psychiatry, McMaster University, Hamilton
*
∗Faculty of Health Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Get access Rights & Permissions [Opens in a new window]

Abstract

Positron emission tomography studies of regional brain metabolic activity, cerebral blood flow and D2 dopamine receptor binding in schizophrenics and controls are reviewed. Methodological influences on the validity of the data generated by these technologies include problems with measurement as well as clinical and anatomical heterogeneity. Work in these fields to date, however, has produced strong support for the role of D2 dopamine receptor blockade in antipsychotic efficacy. Neuroleptic-induced changes in regional brain metabolism over time have also been observed; however, the relationship between such actions and symptomatic change needs to be further clarified. Future studies on time-course of neuroleptic-associated changes in regional brain metabolism, blood flow and dopamine receptor binding in schizophrenics have the potential to provide greater insight into the relationship of these actions to symptomatic changes and drug-induced side-effects.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 163 , Issue S22: The Psychopharmacology of Schizophrenia , December 1993 , pp. 25 - 30
Copyright
Copyright © 1993 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexander, G. E. & Crutcher, M. D. (1990) Functional architecture of basal ganglia circuits; neuronal substrates of parallel processing. Trends in Neuroscience, 13, 266–271.Google Scholar
Andersson, U., Eckernas, S. A., Hartvig, P., et al (1990) Striatal binding of 11C-NMSP studied with positron emission tomography in patients with persistent tardive dyskinesia: no evidence for altered dopamine D2 receptor binding. Journal of Neural Transmission, 7, 215–226.Google Scholar
Bannon, M. J. & Roth, R. H. (1983) Pharmacology of mesocortical dopamine neurons. Pharmacological Reviews, 35, 53–68.Google Scholar
Baron, J. C., Martinot, J. L., Cambon, H., et al (1989) Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels. Psychopharmacology, 99, 463–472.Google Scholar
Bartlett, E. J., Brodie, J. D., Wolf, A.P., et al (1988) Reproducibility of cerebral glucose metabolic measurements in resting human subjects. Journal of Cerebral Blood Flow and Metabolism, 8, 502–512.Google Scholar
Bartlett, E. J., Wolkin, A., Brodie, J. D., et al (1991a) Importance of pharmacologic control in PET studies: effects of thiothixene and haloperidol on cerebral glucose utilization in chronic schizophrenia. Psychiatry Research, 40, 115–124.Google Scholar
Bartlett, E. J., Brodie, J. D., Wolkin, A., et al (19916) The stability of resting deoxyglucose metabolic values in PET studies of schizophrenia. Psychiatry Research, 40, 11–20.Google Scholar
Blin, J., Baron, J. C., Cambon, H., et al (1989) Striatal dopamine D2 receptors in tardive dyskinesia: PET study. Journal of Neurology, Neurosurgery and Psychiatry, 52, 1248–1252.CrossRefGoogle ScholarPubMed
Bouthenet, M. L., Martres, M. P., Sales, N., et al (1987) A detailed mapping of dopamine D2 receptors in rat central nervous system by autoradiography with 125I-iodosulpiride. Neuroscience, 20, 115–155.Google Scholar
Breier, A., Wolkowitz, O. M., Doran, A. R., et al (1987) Neuroleptic responsivity of negative and positive symptoms in schizophrenia. American Journal of Psychiatry, 144, 1549–1555.Google Scholar
Buchsbaum, M. S., Wu, J. C., DeLisi, L., et al (1987) Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: differences between normal controls and schizophrenic patients. Biological Psychiatry, 22, 479–494.Google Scholar
Buchsbaum, M. S., Potkin, S., Marshall, J., et al (1991) Effects of clozapine and thiothixene on glucose metabolic rate in schizophrenia. Neuropsychopharmacology, 6, 155–163.Google Scholar
Cascalla, N. G., Holcomb, H. H., Dixon, L. B., et al (1990) Rate of cerebral glucose metabolism after neuroleptic withdrawal in schizophrenic patients. Biological Psychiatry, 27, 97a.Google Scholar
Cleghorn, J. M., Szechtman, H., Garnett, E. S., et al (1991) Neuroleptic effects on regional brain metabolism in first episode schizophrenics. Schizophrenia Research, 5, 208–210.Google Scholar
Davidson, M. D., Kahn, R. S., Powchik, P., et al (1991) Changes in plasma HVA concentration in schizophrenic patients following neuroleptic discontinuation. Archives of General Psychiatry, 48, 73–76.Google Scholar
DeLisi, L. E., Holcomb, H. H. & Cohen, R. M. (1985) Positron emission tomography in schizophrenic patients with and without neuroleptic medication. Journal of Cerebral Blood Flow and Metabolism, 5, 201–206.Google Scholar
DeLong, M. R. (1990) Primate models of movement disorders of basal ganglia origin. Trends in Neuroscience, 13, 281–285.Google Scholar
Farde, L., Pauli, S., Hall, H., et al (1988a) Stereoselective binding of 11C-raclopride in living human brain: a search for extrastriatal central D2-dopamine receptors by PET. Psychopharmacology, 94, 471–478.Google Scholar
Farde, L., Wiesel, F. A., Halldin, C., et al (1988b) Central D2 dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Archives of General Psychiatry, 45, 71–76.Google Scholar
Farde, L., Wiesel, F. A., Nordstrom, A. L., et al (1989) D1 and D2 dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology, 99, S28–S31.Google Scholar
Farde, L., Nordstrom, A. L., Wiesel, F. A., et al (1992) Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side-effects. Archives of General Psychiatry, 49, 538–544.Google Scholar
Friston, K. J., Frith, C. D., Liddle, P. F., et al (1990) The relationship between global and local changes in PET scans. Journal of Cerebral Blood Flow and Metabolism, 10, 458–466.Google Scholar
Gur, R. E., Resinick, S. M., Gur, R. C., et al (1987) Regional brain function in schizophrenia: II. Repeated evaluation with positron emission tomography. Archives of General Psychiatry, 44, 126–129.Google Scholar
Jenner, P. & Marsden, C.D. (1987) Chronic pharmacological manipulation of dopamine receptors in brain. Neuropharmacology, 26, 931–940.Google Scholar
List, S. & Seeman, P. (1979) Dopamine agonists reverse elevated 3H-neuroleptic binding in neuroleptic pretreated rats. Life Sciences, 24, 1447–1452.Google Scholar
Meltzer, H. Y., Matsubara, S. & Lee, J. C. (1989) The ratios of serotonin-2 and dopamine-2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacology Bulletin, 25, 390–392.Google Scholar
Meltzer, H. Y. & Stockmeier, C. A. (1992) In vivo occupancy of dopamine receptors by antipsychotic drugs. Archives of General Psychiatry, 49, 588–589.Google Scholar
Nordstrom, A.-L., Farde, L. & Halldin, C. (1992) Time course of D2-dopamine receptor occupancy examined by PET after single oral doses of haloperidol. Psychopharmacology, 106, 433–438.Google Scholar
Ohman, R., Larsson, M., Nilsson, I. M., et al (1977) Neurometabolic and behavioural effects of haloperidol in relation to drug levels in serum and brain. Naunym–Schmiedeberg's Archives of Pharmacology, 299, 105–114.Google Scholar
Pickar, D. (1988) Perspectives on a time dependent model of neuroleptic action. Schizophrenia Bulletin, 114, 255–258.Google Scholar
Pickar, D., Labarca, R., Doran, A., et al (1986) Longitudinal measurement of plasma homovanillic acid levels in schizophrenic patients. Archives of General Psychiatry, 43, 669–676.Google Scholar
Pisa, M. (1988) Motor functions of the striatum in the rat: critical role of lateral region in tongue and forelimb reaching. Neuroscience, 24, 453–463.Google Scholar
Resnick, S. M., Gur, R. E., Alavi, A., et al (1988) PET and subcortical glucose metabolism in schizophrenia. Psychiatric Research, 14, 1–11.Google Scholar
Rupniak, N. M., Kilpatrick, G., Hall, M. D., et al (1984) Differential alterations in striatal dopamine receptor sensitivity induced by repeated administration of clinically equivalent doses of haloperidol, sulpiride or clozapine in rats. Psychopharmacology, 84, 512–519.CrossRefGoogle ScholarPubMed
Seeman, P. (1980) Brain dopamine receptors. Pharmacological Reviews, 32, 229–313.Google ScholarPubMed
Seeman, P. (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse, 1, 133–152.Google Scholar
Seeman, P. (1990) Atypical neuroleptics: role of multiple receptors, endogenous dopamine and receptor linkage. Acta Psychiatrica Scandinavica, 82 (suppl. 358), 14–20.CrossRefGoogle Scholar
Smith, M., Wolf, A. P., Brodie, J. D., et al (1988) Serial [18F] N-methyl-spiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients. Biological Psychiatry, 23, 653–663.Google Scholar
Sokoloff, P., Giros, B., Martres, M. P., et al (1990) Molecular cloning characterization of a novel dopamine receptor (D3) as a target of neuroleptics. Nature, 347, 146–151.Google Scholar
Szechtman, H., Nahmias, C., Garnett, E.S., et al (1988) Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia. Archives of General Psychiatry, 454, 523–532.Google Scholar
Tol, H. H. Van, Bunzow, J. R., Guan, H. C., et al (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature, 350, 610–614.Google Scholar
Volkow, N., Brodie, J. D., Wolf, A. P., et al (1986) Brain metabolism in patients with schizophrenia before and after acute neuroleptic administration. Journal of Neurology, Neurosurgery and Psychiatry, 49, 1199–1202.Google Scholar
Warentkin, S., Nilsson, A., Risberg, J., et al (1990) Regional cerebral blood flow in schizophrenia: repeated studies during a psychotic episode. Psychiatry Research: Neuroimaging, 35, 27–38.Google Scholar
Wik, G., Wiesel, F. A., Sjogren, I., et al (1989) Effects of sulpiride and chlorpromazine on regional cerebral glucose metabolism in schizophrenia patients as determined by positron emission tomography. Psychopharmacology, 97, 309–318.Google Scholar
Wolkin, A., Jaeger, J., Brodie, J. D., et al (1985) Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography. American Journal of Psychiatry, 142, 564–571.Google Scholar
Wolkin, A., Barouche, F., Wolf, A. P., et al (1989) Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. American Journal of Psychiatry, 147, 905–908.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.