Dyskinesia pp 174-181 | Cite as

Differential Alteration of Striatal D-1 and D-2 Receptors Induced by the Long-Term Administration of Haloperidol, Sulpiride or Clozapine to Rats

  • P. Jenner
  • N. M. J. Rupniak
  • C. D. Marsden
Part of the Psychopharmacology Supplementum book series (PSYCHOPHARM, volume 2)

Abstract

Rats received haloperidol, sulpiride, or clozapine in their daily drinking water for up to 1 year in clinically equivalent doses. After 12 months’ drug intake, and while drug administration continued, striatal dopamine function was assessed. Haloperidol induced D-2 receptor hypersensitivity as shown by enhanced apomorphine-induced stereotypy, elevated Bmax for specific 3H-spiperone and 3H-NPA binding, and an increase in striatal acetylcholine content. D-1 receptor sites appeared unaffected, since dopamine-stimulated adenylate cyclase and specific 3H-piflutixol binding were not altered. In contrast, neither sulpiride nor clozapine enhanced apomorphine-induced stereotypy or increased Bmax for 3H-spiperone binding. Sulpiride, but not clozapine, increased Bmax for 3H-NPA binding; clozapine, but not sulpiride, elevated striatal acetyl choline concentrations. In general, both sulpiride and clozapine enhanced D-1 function as assessed by dopamine-stimulated adenylate cyclase or 3H-piflutixol binding. On acute administration sulpiride and clozapine appear to act at D-2 sites, but continuous chronic administration of these compounds does not result in the development of striatal D-2 receptor hypersensitivity. The absence of change in D-2 function during chronic treatment, coupled with an ability to enhance D-1 function, may contribute to the low incidence of tardive dyskinesia produced by these drugs in man.

Keywords

Dopamine Schizophrenia Neurol Choline Catecholamine 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • P. Jenner
  • N. M. J. Rupniak
  • C. D. Marsden
    • 1
  1. 1.MRC Movement Disorders Research Group, University Department of Neurology and Parkinsons Disease Society Research CentreInstitute of Psychiatry and Kings College Hospital Medical SchoolLondonEngland

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